Email: igor.popa@upol.cz
Adresa: 17. listopadu 12, 771 46 Olomouc
Telefon: (+420) 58563 4497
Fax: (+420) 58563 4357
Publications
2011
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M. Kubala, J. Vacek, I. Popa, M. Janovska, P. Kosina, J. Ulrichova, Z. Travnicek, and V. Simanek, “The fluorescence properties and NMR analysis of protopine and
allocryptopine,” JOURNAL OF LUMINESCENCE, vol. 131, iss. 7, pp. 1340-1345, 2011.
[Bibtex]@article ISI:000291132900016, Author = Kubala, Martin and Vacek, Jan and Popa, Igor and Janovska, Marika and Kosina, Pavel and Ulrichova, Jitka and Travnicek, Zdenek and Simanek, Vilim, Title = The fluorescence properties and NMR analysis of protopine and allocryptopine, Journal = JOURNAL OF LUMINESCENCE, Year = 2011, Volume = 131, Number = 7, Pages = 1340-1345, Month = JUL, Abstract = The fluorescence properties of protopine and allocryptopine in aqueous and organic environments are described for the first time. The fluorescence of alkaloids and their pH-dependent interconversion to cationic forms (transannular interaction) were studied using steady-state and time-resolved fluorescence techniques. For the analysis of tricyclic base and cis/trans tetracyclic cations of the alkaloids, NMR and X-ray crystallography were used. (C) 2011 Elsevier B.V. All rights reserved., DOI = 10.1016/j.jlumin.2011.02.038, ISSN = 0022-2313, Unique-ID = ISI:000291132900016, - R. Novotna, I. Popa, and Z. Travnicek, “Zinc(II) chlorido complexes of protonated kinetin and its derivatives:
Synthesis, properties and X-ray structure of [Zn(Hkinetin)Cl(3)]center
dot kinetin,” INORGANICA CHIMICA ACTA, vol. 365, iss. 1, pp. 113-118, 2011.
[Bibtex]@article ISI:000285624200017, Author = Novotna, Radka and Popa, Igor and Travnicek, Zdenek, Title = Zinc(II) chlorido complexes of protonated kinetin and its derivatives: Synthesis, properties and X-ray structure of [Zn(Hkinetin)Cl(3)]center dot kinetin, Journal = INORGANICA CHIMICA ACTA, Year = 2011, Volume = 365, Number = 1, Pages = 113-118, Month = JAN 15, Abstract = The syntheses and characterization of five novel zinc(II) complexes with protonated kinetin (6-furfurylaminopurine) and its derivatives are described. Based on the results following from elemental analyses (C, H, N), FTIR, Raman, (1)H and (13)C NMR spectroscopy, conductivity measurements, thermogravimetric (TG) and differential thermal analyses (DTA), and single crystal X-ray analysis, the complexes of the general composition [Zn(HL(n))Cl(3)]center dot xL(n) (1-5) have been prepared, where L(1) = kinetin (6-furfurylaminopurine), L(2) = 6-(5-methylfurfurylamino) purine, L(3) = 2-chloro-6-furfurylaminopurine, L(4) = 2-chloro-6-(5-methylfurfurylamino) purine and L(5) = 2-chloro-6-furfurylamino-9-isopropylpurine, and x = 1/2-2. The structure of [Zn(HL(1))Cl(3)]center dot L(1) (1) has been determined by single crystal X-ray analysis. The Zn(II) atom is tetrahedrally coordinated by three chlorido ligands and one N3-protonated organic molecule forming a ZnCl(3)N donor set. The organic ligand L(1) is coordinated to the Zn(II) centre through the N7 atom of the purine moiety. NMR spectroscopic study confirmed the N3 and N7 atom to be the protonation, and coordination site, respectively. (C) 2010 Elsevier B.V. All rights reserved., DOI = 10.1016/j.ica.2010.08.040, ISSN = 0020-1693, Unique-ID = ISI:000285624200017, - Z. Travnicek, R. Novotna, J. Marek, I. Popa, and M. Sipl, “Transformations of the natural cytokinin N6-isopentenyladenine in
aqueous acidic media: structural aspects,” ORGANIC & BIOMOLECULAR CHEMISTRY, vol. 9, iss. 16, pp. 5703-5713, 2011.
[Bibtex]@article ISI:000293230300015, Author = Travnicek, Zdenek and Novotna, Radka and Marek, Jaromir and Popa, Igor and Sipl, Michal, Title = Transformations of the natural cytokinin N6-isopentenyladenine in aqueous acidic media: structural aspects, Journal = ORGANIC \& BIOMOLECULAR CHEMISTRY, Year = 2011, Volume = 9, Number = 16, Pages = 5703-5713, Abstract = N6-Isopentenyladenine (L1) was subjected to variously acidic media in 0.1 M, 1 M and 2 M HCl. In dependence on the acidity of the medium, the formation of three main acid hydrolysis products, involving the N6-isopentenyladeninium (HL1) (1), 7,8,9,10-tetrahydro-7,7-dimethyl-3H-pyrimido[ 2,1-i]purin-6-ium (HL2) (2) or 5-amino-4-(4,4-dimethyl-3,4,5,6-tetrahydropyrimidin-2-yl)-imidazolium (H(2)L3) (3-5) cations, were determined and characterized by multinuclear solution-state NMR spectroscopy and in the solid state by single crystal X-ray analysis. The coordination abilities of these transformation products have been also investigated. The compounds of the compositions [Zn(HL1)Cl(3)]center dot H(2)O (1), [Zn(3)(HL2)(2)Cl(8)] (2), (H(2)L3)[CuCl(4)] (4) and (H(2)L3)[ZnCl(4)] (5) have been prepared in dependence on the acidity of the medium used by the reactions of L1 with ZnCl(2)center dot 1.5H(2)O or CuCl(2)center dot 2H(2)O. Based on the NMR spectroscopic and X-ray crystallographic results, the mechanism of transformation of L1 in the acidic medium, involving the protonation, cyclization and ring fission, has been suggested., DOI = 10.1039/c1ob05649b, ISSN = 1477-0520, Unique-ID = ISI:000293230300015,
2010
- Z. Travnicek, P. Starha, I. Popa, R. Vrzal, and Z. Dvorak, “Roscovitine-based CDK inhibitors acting as N-donor ligands in the
platinum(II) oxalato complexes: Preparation, characterization and in
vitro cytotoxicity,” EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 45, iss. 10, pp. 4609-4614, 2010.
[Bibtex]@article ISI:000282112700024, Author = Travnicek, Zdenek and Starha, Pavel and Popa, Igor and Vrzal, Radim and Dvorak, Zdenek, Title = Roscovitine-based CDK inhibitors acting as N-donor ligands in the platinum(II) oxalato complexes: Preparation, characterization and in vitro cytotoxicity, Journal = EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, Year = 2010, Volume = 45, Number = 10, Pages = 4609-4614, Month = OCT, Abstract = The reactions of potassium bis(oxalato)platinate dihydrate with two molar equivalents of the potent adenine-based cyclin-dependent kinase inhibitor 2-(1-ethyl-2-hydroxyethylamino)-N6-(benzyl)-9-isopropyladenine (Roscovitine: Ros) and its benzyl-substituted analogues, i.e 2-(1-ethy1-2-hydroxyethylamino)-N6-(2-methoxybenzyl)-9-isopropyladenine (2OMeRos), 2-(1-ethy1-2-hydroxyethylamino)-N6-(3-methoxybenzyl)-9-isopropyladenine (3OMeRos) and 2-(1-ethy1-2-hydroxyethylamino)-N6-(4-methoxybenzyl)-9-isopropyladenine (4OMeRos), were performed and the [Pt(oxXRos)(2)] 3/4 H(2)O (1), [Pt(ox)(2OMeRos)(2)] H(2)O (2), (Pt(ox)(3OMeR-os)(2)] 1/2H(2)O (3) and [Pt(ox)(4OMeRos)(2)] 3/4 H(2)O (4) platinum(II) oxalato complexes were obtained. The methods of the elemental analysis, IR. Raman and NMR spectroscopy, ESI + mass spectrometry, molar conductivity measurement and TG/DTA thermal analysis were performed to characterize the obtained products. The complexes 1-4 Involve tetracoordinated central Pt(11) atom with one bidentate-coordinated oxalate dianion (ox) and two monodentate adenine-based molecules (nRos), thus giving the square-planar geometry around the metal centre with a PtN(2)O(2) donor set. In vitro cytotoxic activity of the complexes against ovarian carcinoma (A2780), cisplatin resistant ovarian carcinoma (A2780cis). malignant melanoma (G-361), lung carcinoma (A549). cervix epitheloid carcinoma (HeLa). breast adenocarcinoma (MCF7) and osteosarcoma (HOS) human cancer cell lines was evaluated. All the tested complexes exceeded the in vitro cytotoxicity of cisplatin and oxaliplatin against HeLa. A2780cis and, except for 2, also against HOS cancer cells The complex 1 was also tested for its cytotoxicity in primary cultures of human hepatocytes and it was not found to be hepatotoxic up to the concentration of 50.0 mu M. (C) 2010 Elsevier Masson SAS. All rights reserved., DOI = 10.1016/j.ejmech.2010.07.025, ISSN = 0223-5234, Unique-ID = ISI:000282112700024, - A. Klanicova, Z. Travnicek, J. Vanco, I. Popa, and Z. Sindelar, “Dinuclear copper(II) perchlorate complexes with 6-(benzylamino)purine
derivatives: Synthesis, X-ray structure, magnetism and antiradical
activity,” POLYHEDRON, vol. 29, iss. 13, pp. 2582-2589, 2010.
[Bibtex]@article ISI:000282389900003, Author = Klanicova, Alena and Travnicek, Zdenek and Vanco, Jan and Popa, Igor and Sindelar, Zdenek, Title = Dinuclear copper(II) perchlorate complexes with 6-(benzylamino)purine derivatives: Synthesis, X-ray structure, magnetism and antiradical activity, Journal = POLYHEDRON, Year = 2010, Volume = 29, Number = 13, Pages = 2582-2589, Month = SEP 3, Abstract = The reactions of Cu(ClO4)(2)center dot 6H(2)O with 6-(benzylamino)purine derivatives in a stoichiometric 1:2 metal-to-ligand ratio led to the formation of penta-coordinated dinuclear complexes of the formula [Cu(2)(mu-L(1-8))(4)(ClO(4))2](ClO(4))(2).nsolv, where L(1) = 6-(2-fluorobenzylamino)purine (complex 1), L(2) = 6-(3-fluorobenzylamino)purine (2), L(3)= 6-(4-fluorobenzylamino)purine (3), L(4)= 6-(2-chlorobenzylamino)purine (4), L(5) = 6-(3-chlorobenzylamino)purine (5), L(6)=6-(4-chlorobenzylamino)purine (6), L(7)= 6-(3-methoxybenzylamino)purine (7) and L(8)= 6-(4-methoxybenzylamino)purine (8); n = 0-4 and solv = H(2)O, EtOH or MeOH. All the complexes have been fully characterized by elemental analysis, FTIR, UV-Vis and EPR spectroscopy, and by magnetic and conductivity measurements. Variable temperature (80-300 K) magnetic susceptibility data of 1-8 showed the presence of a strong antiferromagnetic exchange interaction between two Cu(II) (S= 1/2) atoms with J ranging from -150.0(1) to -160.3(2)cm(-1). The compound 6 center dot 4EtOH center dot H(2)O was structurally characterized by single crystal X-ray analysis. The Cu center dot center dot center dot Cu separation has been found to be 2.9092(8) angstrom. The antiradical activity of the prepared compounds was tested by in vitro SOD-mimic assay with IC(50) in the range 8.67-41.45 mu M. The results of an in vivo antidiabetic activity assay were inconclusive and the glycaemia in pre-treated animals did not differ significantly from the positive control. (C) 2010 Elsevier Ltd. All rights reserved., DOI = 10.1016/j.poly.2010.06.007, ISSN = 0277-5387, Unique-ID = ISI:000282389900003, - L. Dvorak, I. Popa, P. Starha, and Z. Travnicek, “In Vitro Cytotoxic-Active Platinum(II) Complexes Derived from
Carboplatin and Involving Purine Derivatives,” EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, iss. 22, pp. 3441-3448, 2010.
[Bibtex]@article ISI:000281061700006, Author = Dvorak, Lukas and Popa, Igor and Starha, Pavel and Travnicek, Zdenek, Title = In Vitro Cytotoxic-Active Platinum(II) Complexes Derived from Carboplatin and Involving Purine Derivatives, Journal = EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Year = 2010, Number = 22, Pages = 3441-3448, Month = AUG, Abstract = Six platinum(II) complexes of the general formula [Pt(cbdc)-(HL(n))(2)] (1-6; cbdc = cyclobutane-1,1-dicarboxylate and HL(1)-HL(6) = benzyl-substituted 6-benzylamino-2-chloro-9-iso-propylpurine derivatives) have been synthesized by the reaction of [Pt(cbdc)(dmso)(2)] with the corresponding HL(n) compound. The prepared complexes were characterized by elemental analysis and FTIR, Raman and NMR ((1)H, (13)C, (15)N and (195)Pt) spectroscopy. Based on the results of these techniques, it can be concluded that the central Pt(II) atom of the complexes 1-6 is coordinated to two oxygen atoms originating from the cyclobutane-1,1-dicarboxylate group and to two nitrogen atoms from two HL(n) molecules, that is, having a PtN(2)O(2) donor set. Detailed multinuclear and two-dimensional NMR studies indicated the N-7 atom to be the coordination site of the purine derivatives. The coordination mode was proven by a single-crystal X-ray analysis of the [Pt(cbdc)(dmso)-(HL(7))]center dot H(2)O (7a center dot H(2)O) intermediate [HL(7) = 2-chloro-6-(2-methoxybenzyl)amino-9-isopropylpurine]. The geometry is slightly distorted square-planar and the central Pt(II) atom is coordinated to one bidentate cyclobutane-1,1-dicarboxylate dianion, one dmso molecule through the sulfur atom and one HL7 molecule through the N-7 atom of the purine ring, that is, with a PtNO(2)S donor set. The complexes 1-6 were tested for their in vitro cytotoxicity against K-562 (chronic myelogenous leukaemia) and MCF7 (breast adenocarcinoma) human cancer cell lines. Values of IC(50) (drug concentrations lethal for 50\% of the tumour cells) ranged from 4.5 to 14.1 mu m for the K-562 cells and from 4.3 to 21.0 mu m for the MCF7 cells. The in vitro cytotoxicities were in several cases comparable or even higher than those of therapeutically used platinum-based anticancer drugs, that is, cisplatin, carboplatin and oxaliplatin., DOI = 10.1002/ejic.201000322, ISSN = 1434-1948, Unique-ID = ISI:000281061700006, - R. Novotna, Z. Travnicek, and I. Popa, “Synthesis and characterization of the first zinc(II) complexes involving
kinetin and its derivatives: X-ray structures of
2-chloro-N6-furfuryl-9-isopropyladenine and
[Zn(kinetin)(2)Cl(2)]center dot CH(3)OH,” INORGANICA CHIMICA ACTA, vol. 363, iss. 10, pp. 2071-2079, 2010.
[Bibtex]@article ISI:000278592200003, Author = Novotna, Radka and Travnicek, Zdenek and Popa, Igor, Title = Synthesis and characterization of the first zinc(II) complexes involving kinetin and its derivatives: X-ray structures of 2-chloro-N6-furfuryl-9-isopropyladenine and [Zn(kinetin)(2)Cl(2)]center dot CH(3)OH, Journal = INORGANICA CHIMICA ACTA, Year = 2010, Volume = 363, Number = 10, Pages = 2071-2079, Month = JUN 20, Abstract = A series of the first zinc(II) complexes of the general composition [Zn(L(n))(2)Cl(2)]center dot xSolv (1-5) involving kinetin [N6-furfuryladenine, L(1), xSolv = CH(3)OH, complex 1] and its derivatives, i.e. N6-(5-methylfurfuryl)adenine (L(2), xSolv = 2H(2)O, 2), 2-chloro-N6-furfuryladenine (L(3), 3), 2-chloro-N6-(5-methylfurfuryl)adenine (L(4), 4) and 2-chloro-N6-furfuryl-9-isopropyladenine (L(5), 5), as N-donor ligands has been synthesized. The complexes have been fully characterized by elemental analyses (C, H, N), FTIR, Raman, (1)H and (13)C NMR spectroscopy, conductivity measurements, thermogravimetric (TG) and differential thermal (DTA) analyses. Single crystal X-ray analysis determined the molecular structures of 2-chloro-N6-furfuryl-9-isopropyladenine (L(5)) and the complex [Zn(L(1))(2)Cl(2)]center dot CH(3)OH. The Zn(II) ion is tetrahedrally coordinated by two chlorido ligands and two molecules of the L(1) organic compound. The two ligands L(1) are coordinated to the central Zn(II) ion via the N7 atoms. This conclusion can also be drawn from multinuclear NMR spectroscopic experiments. (C) 2010 Elsevier B.V. All rights reserved., DOI = 10.1016/j.ica.2010.02.004, ISSN = 0020-1693, Unique-ID = ISI:000278592200003, - P. Starha, Z. Travnicek, and I. Popa, “Platinum(II) oxalato complexes with adenine-based carrier ligands
showing significant in vitro antitumor activity,” JOURNAL OF INORGANIC BIOCHEMISTRY, vol. 104, iss. 6, pp. 639-647, 2010.
[Bibtex]@article ISI:000277946300004, Author = Starha, Pavel and Travnicek, Zdenek and Popa, Igor, Title = Platinum(II) oxalato complexes with adenine-based carrier ligands showing significant in vitro antitumor activity, Journal = JOURNAL OF INORGANIC BIOCHEMISTRY, Year = 2010, Volume = 104, Number = 6, Pages = 639-647, Month = JUN, Abstract = [Pt(L)(2)(ox)] (1), [Pt(2-OMeL)(2)(ox)] (2), [Pt(3-OMeL)(2)(ox)] (3), [Pt(2,3-diOMeL)(2)(ox)] (4), [Pt(2,4-diOMeL)(2)(ox)] (5), [Pt(3,4-diOMeL)(2)(ox)] (6) and [Pt(3,5-diOMeL)(2)(ox)]center dot 4H(2)O (7) platinum(II) oxalato (ox) complexes were synthesized using the reaction of potassium bis(oxalato)platinate(II) dihydrate with 2-chloro-N6-(benzyl)-9-isopropyladenine or its benzyl-substituted analogues (nL). The complexes 1-7, which represent the first platinum(II) oxalato complexes involving adenine-based ligands, were fully characterized by various physical methods including multinuclear and two dimensional NMR spectroscopy. A single-crystal X-ray analysis of [Pt(2,4-diOMeL)(2)(ox)]center dot 2DMF (5 center dot 2DMF; DMF=N,N'-dimethylformamide), proved the slightly distorted square-planar geometry in the vicinity of the Pt(II) ion with one bidentate-coordinated oxalate dianion and two adenine derivatives (nL) coordinated to the Pt(II) centre through the N7 atom of an adenine moiety, thereby giving a PtN(2)O(2) donor set. In vitro cytotoxicity of the prepared complexes was tested by an MTT assay against osteosarcoma (HOS) and breast adenocarcinoma (MCF7) human cancer cell lines. The best results were achieved for the complexes 2 and 5 in the case of both cell lines, whose IC(50) values equalled 3.6 +/- 1.0, and 4.3 +/- 2.1 mu M (for 2), and 5.4 +/- 3.8, and 3.6 +/- 2.1 mu M (for 5), respectively. The IC(50) equals 9.2 +/- 1.5 mu M against MCF7 cells in the case of 1. The in vitro cytotoxicity of the mentioned complexes significantly exceeded commercially used platinum-based anticancer drugs cisplatin (34.2 +/- 6.4 mu M and 19.6 +/- 4.3 mu M) and oxaliplatin (>50.0 mu M for both cancer cell lines). (C) 2010 Elsevier Inc. All rights reserved., DOI = 10.1016/j.jinorgbio.2010.02.005, ISSN = 0162-0134, Unique-ID = ISI:000277946300004, - J. Nisler, M. Zatloukal, I. Popa, K. Dolezal, M. Strnad, and L. Spichal, “Cytokinin receptor antagonists derived from 6-benzylaminopurine,” PHYTOCHEMISTRY, vol. 71, iss. 7, pp. 823-830, 2010.
[Bibtex]@article ISI:000277908400016, Author = Nisler, Jaroslav and Zatloukal, Marek and Popa, Igor and Dolezal, Karel and Strnad, Miroslav and Spichal, Lukas, Title = Cytokinin receptor antagonists derived from 6-benzylaminopurine, Journal = PHYTOCHEMISTRY, Year = 2010, Volume = 71, Number = 7, Pages = 823-830, Month = MAY, Abstract = Recently we reported 6-(2-hydroxy-3-methylbenzylamino)purine (PI-55) as the first molecule to antagonize cytokinin activity at the receptor level. Here we report the synthesis and in vitro biological testing of eleven BAP derivatives substituted in the benzyl ring and in the C2, N7 and N9 positions of the purine moiety. The ability of the compounds to interact with Arabidopsis cytokinin receptors AHK3 and CRE1/AHK4 was tested in bacterial receptor and in live-cell binding assays, and in an Arabidopsis ARR5:GUS (Arabidopsis response regulator 5) reporter gene assay. Cytokinin activity of the compounds was determined in classical cytokinin biotests (tobacco callus, wheat leaf senescence and Amaranthus bioassays). 6(2,5-Dihydroxybenzylamino)purine (LGR-991) was identified as a cytokinin receptor antagonist. At the molecular level LGR-991 blocks the cytokinin receptor CRE1/AHK4 with the same potency as PI-55. Moreover, LGR-991 acts as a competitive inhibitor of ANK3, and importantly shows reduced agonistic effects in comparison to PI-55 in the ARR5:GUS reporter gene assay and in cytokinin bioassays. LGR-991 causes more rapid germination of Arabidopsis seeds and increases hypocotyl length of dark-grown seedlings, which are characteristics of plants with a reduced cytokinin status. LGR-991 exhibits a structural motive that might lead to preparation of cytokinin antagonists with a broader specificity and reduced agonistic properties. (C) 2010 Elsevier Ltd. All rights reserved., DOI = 10.1016/j.phytochem.2010.01.018, ISSN = 0031-9422, Unique-ID = ISI:000277908400016, - P. Starha, I. Popa, and Z. Travnicek, “Palladium(II) oxalato complexes involving
N6-(benzyl)-9-isopropyladenine-based N-donor carrier ligands: Synthesis,
general properties, (1)H, (13)C and (15)N\(1)H\ NMR characterization
and in vitro cytotoxicity,” INORGANICA CHIMICA ACTA, vol. 363, iss. 7, pp. 1469-1478, 2010.
[Bibtex]@article ISI:000276190300021, Author = Starha, Pavel and Popa, Igor and Travnicek, Zdenek, Title = Palladium(II) oxalato complexes involving N6-(benzyl)-9-isopropyladenine-based N-donor carrier ligands: Synthesis, general properties, (1)H, (13)C and (15)N\(1)H\ NMR characterization and in vitro cytotoxicity, Journal = INORGANICA CHIMICA ACTA, Year = 2010, Volume = 363, Number = 7, Pages = 1469-1478, Month = APR 20, Abstract = Reactions of potassium bis(oxalato)palladate dihydrate, K(2)[Pd(ox)(2)]center dot 2H(2)O, with two molar equivalents of N6-(benzyl)-9-isopropyladenine-based organic molecules (L(1-7)), i.e. 2-chloro-N6-(2-methoxybenzyl)-9-isopropyladenine (L(1)), 2-chloro-N6-(3-methoxybenzyl)-9-isopropyladenine (L(2)), 2-chloro-N6-(3,5-dimethoxybenzyl)-9-isopropyladenine (L(3)), 2-(1-ethyl-2-hydroxyethylamino)-N6-(benzyl)-9-isopropyladenine (L(4)), 2-(1-ethyl-2-hydroxyethylamino)-N6-(2-methoxybenzyl)-9-isopropyladenine (L(5)), 2-(1-ethyl-2-hydroxyethylamino)-N6-(3-methoxybenzyl)-9-isopropyladenine (L(6)) and 2-(1-ethyl-2-hydroxyethylamino)-N6-(4-methoxybenzyl)-9-isopropyladenine (L(7)), provided a series of seven palladium(II) oxalato (ox) complexes of the general formula [Pd(ox)(L(1-7))(2)]center dot nH(2)O (1-7; n = 0 for 4, 5 and 7, (3)/(4) for 1 and 2, 1 for 6, and 3 for 3). The compounds were characterized by elemental analysis, IR, Raman, (1)H, (13)C and (15)N\(1)H\ NMR spectroscopy, ESI+ mass spectrometry, molar conductivity and TG/DTA thermal analysis. The geometry of [Pd(ox)(L(2))(2)] (2) was optimized on the B3LYP/6-311G*/LANL2DZ level of theory. The complexes 4-7 represent the first palladium(II) oxalato complexes with a PdN(2)O(2) donor set, which involve highly potent purine-based cyclin-dependent kinase (CDK) inhibitors (L(4-7)) as carrier N-donor ligands. The selected complexes 1, 3-5 and 7 were tested by an MTT assay for their in vitro cytotoxic activity against human osteosarcoma (HOS) cancer cell line. The highest activity was found for the complexes 5 (IC(50) = 34.9 mu M) and 7 (IC(50) = 39.2 mu M). (C) 2010 Elsevier B.V. All rights reserved., DOI = 10.1016/j.ica.2010.01.035, ISSN = 0020-1693, Unique-ID = ISI:000276190300021, - Z. Travnicek, I. Popa, M. Cajan, R. Zboril, V. Krystof, and J. Mikulik, “The first iron(III) complexes with cyclin-dependent kinase inhibitors:
Magnetic, spectroscopic (IR, ES+ MS, NMR, (57)Fe Mossbauer),
theoretical, and biological activity studies,” JOURNAL OF INORGANIC BIOCHEMISTRY, vol. 104, iss. 4, pp. 405-417, 2010.
[Bibtex]@article ISI:000274921200007, Author = Travnicek, Zdenek and Popa, Igor and Cajan, Michal and Zboril, Radek and Krystof, Vladimir and Mikulik, Jiri, Title = The first iron(III) complexes with cyclin-dependent kinase inhibitors: Magnetic, spectroscopic (IR, ES+ MS, NMR, (57)Fe Mossbauer), theoretical, and biological activity studies, Journal = JOURNAL OF INORGANIC BIOCHEMISTRY, Year = 2010, Volume = 104, Number = 4, Pages = 405-417, Month = APR, Abstract = The first Fe(III) complexes 1-6 with cyclin-dependent kinase (CDK) inhibitors of the type [Fe(L(n))Cl(3)]center dot nH(2)O (n = 0 for 1, 1 for 2, 2 for 3-6; L(1)-L(6) = C2- and phenyl-substituted CDK inhibitors derived from 6-benzyl-amino-9-isopropylpurine), have been synthesized and characterized by elemental analysis, IR, (57)Fe Mossbauer, (1)H and (13)C NMR, and ES+ mass spectroscopies, conductivity and magnetic susceptibility measurements, and thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The study revealed that the compounds are mononuclear, tetrahedral high-spin (S = 5/2) Fe(III) complexes with an admixture of an S = 3/2 spin state originating probably from five-coordinated Fe(III) ions either connecting with a bidentate coordination mode of the CDK inhibitor ligand or relating to the possibility that one crystal water molecule enters the coordination sphere of the central atom in a portion of molecules of the appropriate complex. Nearly spin-only value of the effective magnetic moment (5.82 mu(eff)/mu(B)) was determined for compound 1 due to absence of crystal water molecule(s) in the structure of the complex. Based on NMR data and DFT calculations, we assume that the appropriate organic ligand is coordinated to the Fe(III) ion through the N7 atom of a purine moiety. The cytotoxicity of the complexes was tested in vitro against selected human cancer cell lines (G-361, HOS, K-562 and MCF-7) along with the ability to inhibit the CDK2/cyclinE kinase. The best cytotoxicity (IC(50): 4-23 mu M) and inhibition activity (IC(50): 0.02-0.09 mu M) results have been achieved in the case of complexes 2-4, and complexes 3,4 and 6, respectively. In addition, the X-ray structure of 2-chloro-6-benzylamino-9-isopropylpurine, i.e. a precursor for the preparation of L(1), L(4) and L(5), is also described. (C) 2009 Elsevier Inc. All rights reserved., DOI = 10.1016/j.jinorgbio.2009.12.002, ISSN = 0162-0134, Unique-ID = ISI:000274921200007, - R. Novotna, Z. Travnicek, and I. Popa, “X-ray crystallographic and NMR study of the tautomerism in kinetin,
kinetin riboside and their derivatives: A comparison between the solid
state and solution,” JOURNAL OF MOLECULAR STRUCTURE, vol. 963, iss. 2-3, pp. 202-210, 2010.
[Bibtex]@article ISI:000274867800017, Author = Novotna, Radka and Travnicek, Zdenek and Popa, Igor, Title = X-ray crystallographic and NMR study of the tautomerism in kinetin, kinetin riboside and their derivatives: A comparison between the solid state and solution, Journal = JOURNAL OF MOLECULAR STRUCTURE, Year = 2010, Volume = 963, Number = 2-3, Pages = 202-210, Month = JAN 29, Abstract = N6-furfuryladenine (kinetin, 1), 2-chloro-N6-furfuryladenine (2), N6-furfuryladenosine (kinetin riboside, 3) and 2-chloro-N6-(5-methylfurfuryl)adenosine (4) have been prepared and their structural properties have been studied using a single crystal X-ray analysis (2, 4) and multinuclear 1D and 2D NMR spectroscopy (1-4). The molecular structure of 2 revealed the presence of the 3H-amino and 7H-amino tautomeric forms with the occupancy of 82(3)\%, and 18(3)\%, respectively, for the corresponding hydrogen. The NMR study revealed the presence of tautomeric equilibria in 1, 2 and 4 in dimethyl sulfoxide or N,N'-dimethylformamide solutions at 300 K and 340 K. It has been found that the 9H-amino/7H-amino, 1H,7H-imino/1H,9H-imino and 9H-amino/7H-amino, and amino/1H-imino equilibria exist in 1, 2, and 4, respectively. The presence of a tautomeric equilibrium has not been observed in the case of 3. (c) 2009 Elsevier B.V. All rights reserved., DOI = 10.1016/j.molstruc.2009.10.036, ISSN = 0022-2860, Unique-ID = ISI:000274867800017, - Z. Travnicek, R. Pastorek, P. Starha, I. Popa, and V. Slovak, “Nickel(II) N-Benzyl-N-methyldithiocarbamato Complexes as Precursors for
the Preparation of Graphite Oxidation Accelerators,” ZEITSCHRIFT FUR ANORGANISCHE UND ALLGEMEINE CHEMIE, vol. 636, iss. 8, pp. 1557-1564, 2010.
[Bibtex]@article ISI:000280659500023, Author = Travnicek, Zdenek and Pastorek, Richard and Starha, Pavel and Popa, Igor and Slovak, Vaclav, Title = Nickel(II) N-Benzyl-N-methyldithiocarbamato Complexes as Precursors for the Preparation of Graphite Oxidation Accelerators, Journal = ZEITSCHRIFT FUR ANORGANISCHE UND ALLGEMEINE CHEMIE, Year = 2010, Volume = 636, Number = 8, Pages = 1557-1564, Abstract = The nickel(II) N-benzyl-N-methyldithiocarbantato (BzMedtc) complexes [Ni(BzMedtc)(PPh(3))Cl] (1), [Ni(BzMedtc)(PPh(3))Br] (2), [Ni(BzMedtc)(PPh(3))I] (3), and [Ni(BzMedtc)(PPh(3))(NCS)] (4) were synthesized using the reaction of [Ni(BzMedtc)(2)] and [NiX(2)(PPh(3))(2)] (X = Cl, Br, I and NCS). Subsequently, complex 1 was used for the preparation of [Ni(BzMedtc)(PPh(3))(2)]ClO(4) (5), [Ni(BzMedtc)(PPh(3))(2)]BPh(4) (6), and [Ni(BzMedtc)(PPh(3))(2)]PF(6) (7). The obtained complexes 1-7 were characterized by elemental analysis, thermal analysis and spectroscopic methods (IR, UV/Vis, (31)P\(1)H\ NMR). The results of the magnetochemical and molar conductivity measurements proved the complexes as diamagnetic non-electrolytes (1-4) or 1:1 electrolytes (5-7). The molecular structures of 4 and 5 center dot H(2)O were determined by a single-crystal X-ray analysis. In all cases, the Ni(II) atom is tetracoordinated in a distorted square-planar arrangement with the S(2)PX, and S(2)P(2) donor set, respectively. The catalytic influence of selected complexes 1, 3, 5, and 6 on graphite oxidation was studied. The results clearly indicated that the presence of the products of thermal degradation processes of the mentioned complexes has impact on the course of graphite oxidation. A decrease in the oxidation start temperatures by about 60-100 degrees C was observed in the cases of all the tested complexes in comparison with pure graphite., DOI = 10.1002/zaac.201000091, ISSN = 0044-2313, Unique-ID = ISI:000280659500023,
2009
- M. Siller, P. Anzenbacher, E. Anzenbacherova, K. Dolezal, I. Popa, and M. Strnad, “Interactions of olomoucine II with main drug-metabolizing enzymes of
human liver microsomal fraction,” TOXICOLOGY LETTERS, vol. 189, pp. S108, 2009.
[Bibtex]@article ISI:000269778800315, Author = Siller, Michal and Anzenbacher, Pavel and Anzenbacherova, Eva and Dolezal, Karel and Popa, Igor and Strnad, Miroslav, Title = Interactions of olomoucine II with main drug-metabolizing enzymes of human liver microsomal fraction, Journal = TOXICOLOGY LETTERS, Year = 2009, Volume = 189, Pages = S108, Month = SEP 13, Note = 46th Congress of the European-Societies-of-Toxicology, Dreden, GERMANY, SEP 13-16, 2009, Organization = European Soc Toxicol, DOI = 10.1016/j.toxlet.2009.06.349, ISSN = 0378-4274, Unique-ID = ISI:000269778800315, - P. Starha, Z. Travnicek, and I. Popa, “Synthesis, characterization and in vitro cytotoxicity of the first
palladium(II) oxalato complexes involving adenine-based ligands,” JOURNAL OF INORGANIC BIOCHEMISTRY, vol. 103, iss. 7, pp. 978-988, 2009.
[Bibtex]@article ISI:000267768200006, Author = Starha, Pavel and Travnicek, Zdenek and Popa, Igor, Title = Synthesis, characterization and in vitro cytotoxicity of the first palladium(II) oxalato complexes involving adenine-based ligands, Journal = JOURNAL OF INORGANIC BIOCHEMISTRY, Year = 2009, Volume = 103, Number = 7, Pages = 978-988, Month = JUL, Abstract = The first [Pd(L(n))(2)(ox)] xH(2)O oxalato(ox) complexes involving 2-chloro-N6-(benzyl)-9-isopropyladenine (L(1): complex 1), 2-chloro-N6-(4-methoxybenzyl)-9-isopropyladenine (L(2); 2), 2-chloro-N6-(2,3-dimethoxybenzyl)-9-isopropyladenine (L(3); 3), 2-chloro-N6-(2,4-dimethoxybenzyl)-9-isopropyladenine (L(4); 4), and 2-chloro-N6-(4-methylbenzyl)-9-isopropyladenine (L(5); 5) have been synthesized by the reactions of potassium bis(oxalato)palladate(II) dihydrate, [K(2)Pd(ox)(2)]center dot 2H(2)O, with the mentioned organic compounds (H(2)ox = oxalic acid; x = 0 for 1-3 and 5 or 2 for 4). Elemental analyses (C, H, N), FTIR, Raman and NMR ((1)H, (13)C, (15)N) spectroscopies, conductivity measurements and thermal studies (thermogravimetric and differential thermal analyses, TG/DTA) have been used to characterize the prepared complexes. The molecular structures of [Pd(L(2))(2)(ox)] (2) and [Pd(L(5))(2)(ox)]center dot L(5)center dot Me(2)CO (5 center dot L(5)center dot Me(2)CO) have been determined by a single crystal X-ray analysis. The geometry of these complexes is slightly distorted square-planar with two appropriate L(n) (n = 2 or 5) molecules mutually arranged in the head-to-head (2) or head-to-tail (5) orientation. The L(n) ligands are coordinated to the central Pd(II) ion via the N7 atoms. The same conclusions regarding the binding properties of L(1)-L(5) ligands can be made based on multinuclear NMR spectra. In vitro cytotoxicity of the complexes 1-5 has been evaluated against human chronic myelogenous leukaemia (K562) and human breast adenocarcinoma (MCF7) cancer cell lines. Significant cytotoxicity has been determined for the complexes 3 (IC(50) = 6.2 mu M) and 5 (IC(50) m 6.8 mu M) on the MCF7 cell line, which is even better than that found for the well-known and widely-used platinum-bearing antineoplastic drugs, i.e. oxaliplatin and cisplatin. (C) 2009 Elsevier Inc. All rights reserved., DOI = 10.1016/j.jinorgbio.2009.04.008, ISSN = 0162-0134, Unique-ID = ISI:000267768200006, - L. Spichal, T. Werner, I. Popa, M. Riefler, T. Schmelling, and M. Strnad, “PI-55 is a purine-derived cytokinin antagonist that blocks cytokinin
action via receptor inhibition,” FEBS JOURNAL, vol. 276, pp. 390-391, 2009.
[Bibtex]@article ISI:000267069901194, Author = Spichal, L. and Werner, T. and Popa, I. and Riefler, M. and Schmelling, T. and Strnad, M., Title = PI-55 is a purine-derived cytokinin antagonist that blocks cytokinin action via receptor inhibition, Journal = FEBS JOURNAL, Year = 2009, Volume = 276, Pages = 390-391, Month = JUL, Note = 34th Congress of the Federation-of-European-Biochemical-Societies, Prague, CZECH REPUBLIC, JUL 04-09, 2009, Organization = Federat European Biochem Soc, ISSN = 1742-464X, Unique-ID = ISI:000267069901194, - M. Siller, P. Anzenbacher, E. Anzenbacherova, K. Dolezal, I. Popa, and M. Strnad, “Interactions of Olomoucine II with Human Liver Microsomal Cytochromes
P450,” DRUG METABOLISM AND DISPOSITION, vol. 37, iss. 6, pp. 1198-1202, 2009.
[Bibtex]@article ISI:000266147500008, Author = Siller, Michal and Anzenbacher, Pavel and Anzenbacherova, Eva and Dolezal, Karel and Popa, Igor and Strnad, Miroslav, Title = Interactions of Olomoucine II with Human Liver Microsomal Cytochromes P450, Journal = DRUG METABOLISM AND DISPOSITION, Year = 2009, Volume = 37, Number = 6, Pages = 1198-1202, Month = JUN, Abstract = Olomoucine II is a cyclin-dependent kinase inhibitor and a potential antineoplastic agent because it can arrest animal cell cycles. This study examines its interactions with human liver microsomal cytochrome P450 (P450) enzymes. Spectroscopic and high-performance liquid chromatography (HPLC) methods were used to estimate the degree of olomoucine II-mediated inhibition of enzymatic activities of eight drug-metabolizing P450s in vitro. In addition, mass spectrometry coupled with HPLC was used to identify an olomoucine II metabolite (2,5-dihydroxyroscovitine) formed in the reaction mixtures, and CYP3A4 was found to be responsible for the hydroxylation of the N(6)-benzyl ring at position 5, leading to this compound. Olomoucine II significantly inhibited the enzymatic activities of CYP1A2, CYP2C9, and (to a lesser degree) CYP3A4. The results indicate that use of olomoucine II as a drug could affect the activities of CYP3A4, CYP1A2, and CYP2C9 in vivo. Hence, the clinical relevance of these interactions should be carefully evaluated., DOI = 10.1124/dmd.108.025502, ISSN = 0090-9556, Unique-ID = ISI:000266147500008, - L. Szucova, L. Spichal, K. Dolezal, M. Zatloukal, J. Greplova, P. Galuszka, V. Krystof, J. Voller, I. Popa, F. J. Massino, J. Jorgensen, and M. Strnad, “Synthesis, characterization and biological activity of ring-substituted
6-benzylamino-9-tetrahydropyran-2-yl and 9-tetrahydrofuran-2-ylpurine
derivatives,” BIOORGANIC & MEDICINAL CHEMISTRY, vol. 17, iss. 5, pp. 1938-1947, 2009.
[Bibtex]@article ISI:000264067900020, Author = Szucova, Lucie and Spichal, Lukas and Dolezal, Karel and Zatloukal, Marek and Greplova, Jarmila and Galuszka, Petr and Krystof, Vladimir and Voller, Jiri and Popa, Igor and Massino, Frank J. and Jorgensen, Jan-Elo and Strnad, Miroslav, Title = Synthesis, characterization and biological activity of ring-substituted 6-benzylamino-9-tetrahydropyran-2-yl and 9-tetrahydrofuran-2-ylpurine derivatives, Journal = BIOORGANIC \& MEDICINAL CHEMISTRY, Year = 2009, Volume = 17, Number = 5, Pages = 1938-1947, Month = MAR 1, Abstract = In an attempt to improve specific biological functions of cytokinins routinely used in plant micropropagation, 33 6-benzylamino-9-tetrahydropyran-2-ylpurine (THPP) and 9-tetrahydrofuran-2-ylpurine (THFP) derivatives, with variously positioned hydroxy and methoxy functional groups on the benzyl ring, were prepared. The new derivatives were prepared by condensation of 6-chloropurine with 3,4-dihydro-2H-pyran or 2,3-dihydrofuran and then by the condensation of these intermediates with the corresponding benzylamines. The prepared compounds were characterized by elemental analyses, TLC, HPLC, melting point determinations, CI+ MS and (1)H NMR spectroscopy. The cytokinin activity of all the prepared derivatives was assessed in three classical cytokinin bioassays (tobacco callus, wheat leaf senescence and Amaranthus bioassay). The derivatives 6-(3-hydroxybenzylamino)-9-tetrahydropyran-2-ylpurine (3) and 6-(3-hydroxybenzylamino)-9-tetrahydrofuran-2-ylpurine (23) were selected, because of the high affinity of their parent compound meta-topolin (mT, 6-(3-hydroxybenzylamino) purine) to cytokinin receptors, as model compounds for studying their perception by the receptors CRE1/AHK4 and AHK3 in a bacterial assay. Both receptors perceived these two derivatives less well than they perceived the parent compound. Subsequently, the susceptibility of several new derivatives to enzyme degradation by cytokinin oxidase/dehydrogenase was studied. Substitution of tetrahydropyran-2-yl (THP) at the N(9) position decreased the turnover rates of all new derivatives to some extent. To provide a practical perspective, the cytotoxicity of the prepared compounds against human diploid. broblasts (BJ) and the human cancer cell lines K-562 and MCF-7 was also assayed in vitro. The prepared compounds showed none or marginal cytotoxicity compared to the corresponding N(9)-ribosides. Finally, the pH stability of the two model compounds was assessed in acidic and neutral water solutions (pH 3-7) by high-performance liquid chromatography (HPLC). (C) 2009 Elsevier Ltd. All rights reserved., DOI = 10.1016/j.bmc.2009.01.041, ISSN = 0968-0896, Unique-ID = ISI:000264067900020, - P. Starha, Z. Travnicek, R. Herchel, I. Popa, P. Suchy, and J. Vanco, “Dinuclear copper(II) complexes containing 6-(benzylamino)purines as
bridging ligands: Synthesis, characterization, and in vitro and in vivo
antioxidant activities,” JOURNAL OF INORGANIC BIOCHEMISTRY, vol. 103, iss. 3, pp. 432-440, 2009.
[Bibtex]@article ISI:000263693900016, Author = Starha, Pavel and Travnicek, Zdenek and Herchel, Radovan and Popa, Igor and Suchy, Pavel and Vanco, Jan, Title = Dinuclear copper(II) complexes containing 6-(benzylamino)purines as bridging ligands: Synthesis, characterization, and in vitro and in vivo antioxidant activities, Journal = JOURNAL OF INORGANIC BIOCHEMISTRY, Year = 2009, Volume = 103, Number = 3, Pages = 432-440, Month = MAR, Abstract = A series of dinuclear copper(II) complexes involving 6-(benzylamino)purine derivatives, (HL(n)), as bridging ligands were synthesized, characterized and tested for both their in vitro and in vivo antioxidant activities. Based on results of elemental analyses, temperature dependence of magnetic susceptibility measurements, UV-vis, FTIR, EPR, NMR and MALDI-TOF mass spectroscopy, conductivity measurements and thermal analyses, the complexes with general compositions Of [Cu(2)(mu-HL(n))(4)Cl(2)]Cl(2)center dot 2H(2)O (1-4) and [Cu(2)(mu-HL(n))(2)(mu-Cl)(2)Cl(2)] (5-7) were prepared [where n = 1-4; HL(1) = 6-[(2-methoxybenzyl)amino]purine, HL(2) = 6-[(4-methoxybenzyl)amino]purine, HL(3) = 6-[(2,3-dimethoxybenzyl)amino]purine and HL(4) = 6[(3,4-dimethoxybenzyl)amino]purine). In the case of complexes 2, 3, 5 and 7, the antioxidant activities were studied by both in vitro [superoxide dismutase-mimic (SOD-mimic) activity) and in vivo (cytoprotective effect against the alloxan-induced diabetes (antidiabetic activity)) methods. The obtained IC(50) value of the SOD-mimic activity for the complex 5 (IC(50) = 0.253 mu M) was shown to be even better than that of the native bovine Cu,Zn-SOD enzyme (IC(50) = 0.480 mu M), used as a standard. As for the antidiabetic activity, the pretreatment of mice with complexes 3 and 7 led to the complete elimination of cytotoxic attack of alloxan and its free radical metabolites, used as a diabetogenic agent. The cytoprotective effect of these compounds was proved by the preservation of the initial blood glucose levels of the pretreated animals, as against the untreated control group. (C) 2008 Elsevier Inc. All rights reserved., DOI = 10.1016/j.jinorgbio.2008.12.009, ISSN = 0162-0134, Unique-ID = ISI:000263693900016, - L. Spichal, T. Werner, I. Popa, M. Riefler, T. Schmuelling, and M. Strnad, "The purine derivative PI-55 blocks cytokinin action via receptor
inhibition," FEBS JOURNAL, vol. 276, iss. 1, pp. 244-253, 2009.
[Bibtex]@article ISI:000261683900022, Author = Spichal, Lukas and Werner, Tomas and Popa, Igor and Riefler, Michael and Schmuelling, Thomas and Strnad, Miroslav, Title = The purine derivative PI-55 blocks cytokinin action via receptor inhibition, Journal = FEBS JOURNAL, Year = 2009, Volume = 276, Number = 1, Pages = 244-253, Month = JAN, Abstract = One of several potential approaches to study mechanisms of action of biologically active compounds is to develop their agonists and antagonists. In the present study, we report the identification of the first known molecule antagonizing the activity of the plant hormone cytokinin at the receptor level. This compound, 6-(2-hydroxy-3-methylbenzylamino)purine, designated PI-55 in the present study, is structurally closely related to cytokinin 6-benzylaminopurine, but substitutions at specific positions of the aromatic side chain strongly diminished its cytokinin activity and conferred antagonistic properties. PI-55 competitively inhibited the binding of the natural ligand trans-zeatin to the Arabidopsis cytokinin receptors cytokinin response 1 (CRE1)/Arabidopsis histidine kinase (AHK) 4 and AHK3 and repressed induction of the cytokinin response gene ARR5:GUS. Genetic analysis revealed that CRE1/AHK4 is the primary target of PI-55. Cytokinin bioassays also demonstrated the anticytokinin effect of PI-55 in several other species. Furthermore, we show that PI-55 accelerated the germination of Arabidopsis seeds and promoted the root growth and formation of lateral roots, thus phenocopying the known consequences of a lowered cytokinin status and demonstrating its potential to inhibit cytokinin perception in planta. PI-55 is the first example for the targeted development of a cytokinin antagonist and represents an initial step for the preparation of cytokinin antagonists with broad activity and reduced agonistic properties., DOI = 10.1111/j.1742-4658.2008.06777.x, ISSN = 1742-464X, Unique-ID = ISI:000261683900022,
2008
- Z. Travnicek, J. Mikulik, M. Cajan, R. Zboril, and I. Popa, "Novel iron complexes bearing N6-substituted adenosine derivatives:
Synthesis, magnetic, (57)Fe Mossbauer, DFT, and in vitro cytotoxicity
studies," BIOORGANIC & MEDICINAL CHEMISTRY, vol. 16, iss. 18, pp. 8719-8728, 2008.
[Bibtex]@article ISI:000259173400046, Author = Travnicek, Zdenek and Mikulik, Jiri and Cajan, Michal and Zboril, Radek and Popa, Igor, Title = Novel iron complexes bearing N6-substituted adenosine derivatives: Synthesis, magnetic, (57)Fe Mossbauer, DFT, and in vitro cytotoxicity studies, Journal = BIOORGANIC \& MEDICINAL CHEMISTRY, Year = 2008, Volume = 16, Number = 18, Pages = 8719-8728, Month = SEP 15, Abstract = Iron complexes (1-7) involving N6-benzyladenosine derivatives of the predominant composition [Fe(L(n))Cl(3)]center dot H(2)O \where L(1) = N6-(2-fluorobenzyl)adenosine (1), L(2) = N6-(4-fluorobenzyl)adenosine (2), L(3) = N6-(2-trifluoromethylbenzyl)adenosine (3), L(4) = N6-(3-trifluoromethylbenzyl)adenosine (4), L(5) = N6-(4-trifluoromethylbenzyl)adenosine (5), L(6) = N6-(4-trifluoromethoxybenzyl)adenosine (6), and L(7) = N6-(4-chlorobenzyl)adenosine (7)\ have been synthesized. The compounds have been characterized by elemental analysis, variable-temperature and in-field (57)Fe Mossbauer, ES+ MS, FTIR, (1)H and (13)C NMR spectroscopies, magnetochemical and conductivity measurements, thermal (TGA/DSC/DTA) analyses, and DFT calculations. It has been found that the organic molecule is coordinated to iron via N7 atom of the appropriate adenosine derivative and the products are represented by mixtures of complexes with various iron oxidation (Fe(III)/Fe(II)) and spin states (S = 5/2, 4/2, 3/2, 2/2) and geometries (tetrahedral or trigonal bipyramidal). It is caused by the fact that partial redox processes proceed during the reactions due to the presence of a ribose moiety, which is oxidized to the corresponding 5'-ribotic acid, and simultaneously, a portion of Fe(III) cations is reduced to Fe(II) ones. Moreover, a significant effect of crystal water molecules on stereochemistry, and hence, on magnetic and spectral properties of the prepared complexes has been found. The compounds have been tested for their in vitro cytotoxicity against the following human cancer cell lines: malignant melanoma (G-361), osteogenic sarcoma (HOS), chronic myelogenous leukemia (K-562), and breast adenocarcinoma (MCF-7). The most important results have been obtained for complex 2 with IC(50) values 8-16 mu M against HOS, K-562, and MCF-7 cell lines, and for complex 6 with IC50 value 4 mu M against MCF-7 cell line. (C) 2008 Elsevier Ltd. All rights reserved., DOI = 10.1016/j.bmc.2008.07.082, ISSN = 0968-0896, Unique-ID = ISI:000259173400046, - L. Szucova, Z. Travnicek, I. Popa, and J. Marek, "Preparation and cis-to-trans transformation study of square-planar
[Pt(L(n))2Cl(2)] complexes bearing cytokinins derived from
6-benzylaminopurine (L(n)) by view of NMR spectroscopy and X-ray
crystallography," POLYHEDRON, vol. 27, iss. 12, pp. 2710-2720, 2008.
[Bibtex]@article ISI:000258616400029, Author = Szucova, Lucie and Travnicek, Zdenek and Popa, Igor and Marek, Jaromir, Title = Preparation and cis-to-trans transformation study of square-planar [Pt(L(n))2Cl(2)] complexes bearing cytokinins derived from 6-benzylaminopurine (L(n)) by view of NMR spectroscopy and X-ray crystallography, Journal = POLYHEDRON, Year = 2008, Volume = 27, Number = 12, Pages = 2710-2720, Month = AUG 21, Abstract = Mononuclear, square-planar platinum(II) complexes involving derivatives of aromatic cytokinins as the ligands, and having the general formula cis-[Pt(L(n))(2)Cl(2)] (1-3) and trans-[Pt(L(n))(2)Cl(2)] (4-6), where n = 13, L(1) = 2-chloro-6-(benzylamino)-9-isopropylpurine, L(2) = 2-chloro-6-[(4-methoxybenzyl)amino]-9-isopropylpurine and L(3) = 2-chloro-6-[(2-methoxybenzyl)-amino]-9-isopropylpurine, have been synthesized and characterized by elemental analysis, MALDI-TOF mass, FT IR, (1)H, (13)C, (15)N and (195)Pt NMR spectral measurements. Dynamic cis-to-trans isomerization process of complex 1 in N,N'-dimethylformamide (DMF) has been investigated by means of multinuclear NMR spectroscopy. The solid-state structures of 1, 4 center dot (DMF)(2), and 5 have been determined by single crystal X-ray analysis. X-ray structures revealed that the heterocyclic ligands are coordinated to platinum via nitrogen atom N(7) in all the complexes studied. In vitro cytotoxicity of the prepared complexes against MCF7, G361, K562, and HOS has been evaluated. Owing to low solubility of the complexes in water, the cytotoxicity has been only tested up to 5 mu M concentration. Unfortunately, all complexes have been found to be non-cytotoxic in the accessible concentration range., DOI = 10.1016/j.poly.2008.05.021, ISSN = 0277-5387, Unique-ID = ISI:000258616400029,
2007
- Z. Travnicek, I. Popa, M. Cajan, R. Herchel, and J. Marek, "The first platinum(IV) complexes involving aromatic cytokinins or
cyclin-dependent kinase inhibitors derived from 6-benzylaminopurine:
X-ray structures of (BohH(2)(2+))[PtCl6] center dot H2O and
(RosH(2)(2+))(2)[PtCl6]Cl-2 center dot 4H(2)O," POLYHEDRON, vol. 26, iss. 18, pp. 5271-5282, 2007.
[Bibtex]@article ISI:000251617700011, Author = Travnicek, Zdenek and Popa, Igor and Cajan, Michal and Herchel, Radovan and Marek, Jaromir, Title = The first platinum(IV) complexes involving aromatic cytokinins or cyclin-dependent kinase inhibitors derived from 6-benzylaminopurine: X-ray structures of (BohH(2)(2+))[PtCl6] center dot H2O and (RosH(2)(2+))(2)[PtCl6]Cl-2 center dot 4H(2)O, Journal = POLYHEDRON, Year = 2007, Volume = 26, Number = 18, Pages = 5271-5282, Month = NOV 20, Abstract = A series of Pt(IV) complexes with cytokinins or CDK-inhibitors derived from 6-benzylaminopurine (Bap) of the composition [Pt-IV(LH+)Cl-5] (1-14), where LH+ stands for protonated form of the Bap derivative (1-12), Boh = 6-(benzylamino)-2-[(3-hydroxypropyl)amino]-9-isopropylpurine, bohemine (13) and Ros = 6-(benzylamino)-2-[(1-hydroxymethylpropyl)amino]-9-isopropylpurine, roscovitine (14), have been prepared. They have been fully characterized by microanalysis, conductivity, FT-IR, H-1, C-13, N-15 and Pt-195 NMR and ES+ mass spectroscopy. It has been found that the cytokinin molecule is coordinated via N9 atom to platinum(IV) and N1, N7-protonated in case of complexes 1-12, and N7 coordinated and NI-protonated in case of complexes with CDK inhibitors (13 and 14). Predicted molecular geometries of the complexes have been supported by DFT calculations at the B3LYP level with the 6-311+G**/LANL2DZ and aug-cc-pVDZ/LANL2DZ basis sets. All of the compounds have been tested in vitro for their cytotoxicity against four human cancer cell lines: malignant melanoma (G361), osteogenic sarcoma (HOS), chronic myelogenous erythroleukemia (K562) and breast adenocarcinoma (MCF7). The best result has been achieved for complex 14, where IC50 = 17 mu M against K562. The molecular structures of two ionic pair compounds (BohH(2)(2+))[PtCl6] center dot H2O (15) and (RosH(2)(2+))(2)[PtCl6]Cl-2 center dot 4H(2)O (16) have been determined by a single crystal X-ray analysis. (c) 2007 Elsevier Ltd. All rights reserved., DOI = 10.1016/j.poly.2007.07.026, ISSN = 0277-5387, Unique-ID = ISI:000251617700011, - K. Dolezal, I. Popa, E. Hauserova, L. Spichal, K. Chakrabarty, O. Novak, V. Krystof, J. Voller, J. Holub, and M. Strnad, "Preparation, biological activity and endogenous occurrence of
N-6-benzyladenosines," BIOORGANIC & MEDICINAL CHEMISTRY, vol. 15, iss. 11, pp. 3737-3747, 2007.
[Bibtex]@article ISI:000246649000015, Author = Dolezal, Karel and Popa, Igor and Hauserova, Eva and Spichal, Lukas and Chakrabarty, Kuheli and Novak, Ondrej and Krystof, Vladimir and Voller, Jiri and Holub, Jan and Strnad, Miroslav, Title = Preparation, biological activity and endogenous occurrence of N-6-benzyladenosines, Journal = BIOORGANIC \& MEDICINAL CHEMISTRY, Year = 2007, Volume = 15, Number = 11, Pages = 3737-3747, Month = JUN 1, Abstract = Cytokinin activity of forty-eight 6-benzyladenosine derivatives at both the receptor and cellular levels as well as their anticancer properties were compared in various in vitro assays. The compounds were prepared by the condensation of 6-chloropurine riboside with corresponding substituted benzylamines and characterized by standard collection of physico-chemical methods. The majority of synthesized derivatives exhibited high activity in all three of the cytokinin bioassays used (tobacco callus, wheat leaf senescence and Amaranthus bioassay). The highest activities were observed in the senescence bioassay. For several of the compounds tested, significant differences in activity were found between the bioassays used, indicating that diverse recognition systems may operate. This suggests that it may be possible to modulate particular cytokinin-dependent processes with specific compounds. In contrast to their high activity in bioassays, the tested compounds were recognized with only very low sensitivity in both Arabidopsis thaliana AHK3 and AHK4 receptor assays. The prepared derivatives were also investigated for their antiproliferative properties on cancer and normal cell lines. Several of them showed very strong cytotoxic activity against various cancer cell lines. On the other hand, they were not cytotoxic for normal murine fibroblast (NIH/3T3) cell line. This anticancer activity of cytokinin ribosides may be important, given that several of them occur as endogenous compounds in different organisms. (c) 2007 Elsevier Ltd. All rights reserved., DOI = 10.1016/j.bmc.2007.03.038, ISSN = 0968-0896, Unique-ID = ISI:000246649000015, - Z. Travnicek, L. Szucova, and I. Popa, "Synthesis, characterization and assessment of the cytotoxic properties
of cis and trans-[Pd(L)(2)Cl-2] complexes involving
6-benzylamino-9-isopropylpurine derivatives," JOURNAL OF INORGANIC BIOCHEMISTRY, vol. 101, iss. 3, pp. 477-492, 2007.
[Bibtex]@article ISI:000244773800012, Author = Travnicek, Zdenek and Szucova, Lucie and Popa, Igor, Title = Synthesis, characterization and assessment of the cytotoxic properties of cis and trans-[Pd(L)(2)Cl-2] complexes involving 6-benzylamino-9-isopropylpurine derivatives, Journal = JOURNAL OF INORGANIC BIOCHEMISTRY, Year = 2007, Volume = 101, Number = 3, Pages = 477-492, Month = MAR, Abstract = A series of square-planar Pd(II) complexes of the composition cis-[Pd(L-n)(2)Cl-2] \L-1 = 2-chloro-6-benzylamino-9-isopropyipurine (1), L-2 = 2-chloro-6-[(4-methoxybenzyl)amino]-9-isopropylpurine (2), L-3 = 2-chloro-6-[(2-methoxybenzyl)amino]-9-isopropylpurine (3) and 2-[(chloropropyl)aminol-6-benzylamino-9-isopropylpurine (6)] has been synthesized by the reaction of PdCl2 with L-n in a 1:2 molar ratio. In contrast, the same reaction followed by recrystallization of the product from N,N'-dimethylformamide (DMF) leads to trans-[Pd(L-n)(2)Cl-2] - nDMF \L-3, n = 0 (4), n = 1(4*DMF); L-4 = 2-chloro-6-[(2,3-dimethoxybenzyl)-amino]-9-isopropylpurine, n = 0 (5), n = 1.5 (5*DMF). The compounds have been characterized by elemental analyses, conductivity measurements, electrospray mass spectra in the positive ion mode (ES + MS), FTIR, H-1 and C-13 NMR spectra, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Moreover, the complexes 2 and 6 have been also investigated by N-15 NMR spectroscopy. The molecular structures of L-5, \(H2+L5)(Cl-)(2)\ - H2O, i.e. the protonated form of L-5, trans-[Pd(L-3)(2)Cl-2](4) and trans-[Pd(L-4)(2)Cl-2] (5) have been determined by single crystal X-ray analysis. NMR data and X-ray structures revealed that the organic molecules are coordinated to Pd via N7 atom of a purine moiety. All the complexes and the corresponding ligands have been tested in vitro for their cytotoxicity against four human cancer cell lines: breast adenocarcinoma (MCF7), malignant melanoma (G361), chronic myelogenous leukaemia (K562) and osteogenic sarcoma (HOS). Promising in vitro cytotoxic effect has been found for cis-[Pd(L-2)(2)Cl-2] (2), having the IC50 values of 12, 10, 25, and 14 mu M against MCF7, G361, K562, and HOS, respectively, and for trans-[Pd(L-3)(2)Cl-2] - DMF (4) with the IC50 value of 15 mu M against G361. (c) 2006 Elsevier Inc. All rights reserved., DOI = 10.1016/j.jinorgbio.2006.11.010, ISSN = 0162-0134, Unique-ID = ISI:000244773800012, - Z. Travnicek and I. Popa, "2-chloro-6-[(2,6-dimethoxybenzyl)amino]9-isopropylpurine 0.125-hydrate," ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE, vol. 63, iss. Part 2, pp. O629-O631, 2007.
[Bibtex]@article ISI:000245187300247, Author = Travnicek, Zdenek and Popa, Igor, Title = 2-chloro-6-[(2,6-dimethoxybenzyl)amino]9-isopropylpurine 0.125-hydrate, Journal = ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE, Year = 2007, Volume = 63, Number = Part 2, Pages = O629-O631, Month = FEB, Abstract = The secondary structure in the title compound, C17H20ClN5O2 center dot 0.125H(2)O, is stabilized by N-H center dot center dot center dot N hydrogen bonds that connect molecules into centrosymmetric dimers; the dimers are linked via a variety of intermolecular interactions., DOI = 10.1107/S1600536807000268, ISSN = 1600-5368, Unique-ID = ISI:000245187300247, - Z. Travnicek and I. Popa, "2-chloro-6-[(4-hydroxy-3,5-dimethoxybenzyl)amino]-9-isopropylpurine," ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE, vol. 63, iss. Part 2, pp. O728-O730, 2007.
[Bibtex]@article ISI:000245187300291, Author = Travnicek, Zdenek and Popa, Igor, Title = 2-chloro-6-[(4-hydroxy-3,5-dimethoxybenzyl)amino]-9-isopropylpurine, Journal = ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE, Year = 2007, Volume = 63, Number = Part 2, Pages = O728-O730, Month = FEB, Abstract = The structure of the title compound, C17H20ClN5O3, consists of discrete molecules of a 6-(benzylamino) purine derivative. The secondary structure is stabilized by N-(HO)-O-... hydrogen bonds connecting molecules into centrosymmetric dimers and by weak interatomic contacts of the types C-(HCl)-Cl-... and C (HO)-O-...,and by pi-pi stacking interactions., DOI = 10.1107/S1600536807001511, ISSN = 1600-5368, Unique-ID = ISI:000245187300291, - J. Stranska, M. Sebela, P. Tarkowski, P. Rehulka, J. Chmelik, I. Popa, and P. Pec, "Inhibition of plant amine oxidases by a novel series of diamine
derivatives," BIOCHIMIE, vol. 89, iss. 1, pp. 135-144, 2007.
[Bibtex]@article ISI:000243630100012, Author = Stranska, Jana and Sebela, Marek and Tarkowski, Petr and Rehulka, Pavel and Chmelik, Josef and Popa, Igor and Pec, Pavel, Title = Inhibition of plant amine oxidases by a novel series of diamine derivatives, Journal = BIOCHIMIE, Year = 2007, Volume = 89, Number = 1, Pages = 135-144, Month = JAN, Abstract = A series of N,N'-bis(2-pyridinylmethyl)diamines was synthesized and characterized for their inhibition effects towards plant copper-containing amine oxidase (EC 1.4.3.6) and polyamine oxidase (EC 1.5.3.11), which mediate the catabolic regulation of cellular polyamines. Even though these enzymes catalyze related reactions and, among others, act upon two common substrates (spermidine and spermine), their molecular and kinetic properties are different. They also show a different spectrum of inhibitors. It is therefore of interest to look for compounds providing a dual inhibition (i.e. inhibiting both enzymes with the same inhibition potency), which would be useful in physiological studies involving modulations of polyamine catabolism. The synthesized diamine derivatives comprised from two to eight carbon atoms in the alkyl spacer chain. Kinetic measurements with pea (Pisum sativum?) diamine oxidase and oat (Avena sativa) polyamine oxidase demonstrated reversible binding of the compounds at the active sites of the enzymes as they were almost exclusively competitive inhibitors with K-i values ranging from 10(-5) to 10(-3) M. In case of oat polyamine oxidase, the Ki values were significantly influenced by the number of methylene groups in the inhibitor molecule. The measured inhibition data are discussed with respect to enzyme structure. For that reason, the oat enzyme was analyzed by de novo peptide sequencing using mass spectrometry and shown to be homologous to polyamine oxidases from barley (isoform 1) and maize. We cony clude that some of the studied N,N'-bis(2-pyridinylmethyl)diamines might have a potential to be starting structures in design of metabolic modulators targeted to both types of amine oxidases. (c) 2006 Elsevier Masson SAS. All rights reserved., DOI = 10.1016/j.biochi.2006.08.001, ISSN = 0300-9084, Unique-ID = ISI:000243630100012, - F. Sersen, D. Loos, J. Csollei, I. Popa, J. Vanco, and F. Gregan, "Antioxidative activity of potential antihypertensives with dual effect," CHEMICKE LISTY, vol. 101, iss. 1, pp. 60-64, 2007.
[Bibtex]@article ISI:000243899600009, Author = Sersen, Frantisek and Loos, Dusan and Csollei, Jozef and Popa, Igor and Vanco, Jan and Gregan, Fridrich, Title = Antioxidative activity of potential antihypertensives with dual effect, Journal = CHEMICKE LISTY, Year = 2007, Volume = 101, Number = 1, Pages = 60-64, Abstract = The antioxidative properties of four 1-(2-benzofuran2-yl-2-hydroxyethyl)-4-phenylpiperazines were studied by indirect spectrophotometric and direct ESR spin-trap methods. The radical scavenging activity of the tested compounds was determined. The compounds exhibit interesting structure-specific redox properties. Scavenging of DPPH radicals gave very poor results. The studied compounds did not affect the elimination of superoxide anion radicals; however, they caused stimulation of O-2(-.) radical production. The hydroxyl radicals, however, were scavenged only by 2-fluorophenyl derivatives, whereas the 4-fluorophenyl derivatives exhibited a slightly prooxidative effect. The capture of HO. radicals by 2-fluorophenyl derivatives was, according to the results of NMR analyses, attributed to the interaction with non-protonated piperazine nitrogen atom, which is stabilized by the hydrogen bond between the hydroxy group and fluorine atom., ISSN = 0009-2770, Unique-ID = ISI:000243899600009,
2006
- A. Klanicova, Z. Travnicek, I. Popa, M. Cajan, and K. Dolezal, "Synthesis, characterization and in vitro cytotoxicity of Co(II)
complexes with N6-substituted adenine derivatives: X-ray structures of
6-(4-chlorobenzylamino)purin-di-ium diperchlorate dihydrate and
[Co-6(mu-L-6)(4)Cl-8(DMSO)(10)] center dot 4DMSO," POLYHEDRON, vol. 25, iss. 6, pp. 1421-1432, 2006.
[Bibtex]@article ISI:000236698900022, Author = Klanicova, A and Travnicek, Z and Popa, I and Cajan, M and Dolezal, K, Title = Synthesis, characterization and in vitro cytotoxicity of Co(II) complexes with N6-substituted adenine derivatives: X-ray structures of 6-(4-chlorobenzylamino)purin-di-ium diperchlorate dihydrate and [Co-6(mu-L-6)(4)Cl-8(DMSO)(10)] center dot 4DMSO, Journal = POLYHEDRON, Year = 2006, Volume = 25, Number = 6, Pages = 1421-1432, Month = APR 17, Abstract = Cobalt(II) complexes of the composition [Co(L-1)Cl(H2O)(2)]center dot H2O (1), [Co(L-2)Cl(H2O)(2)]center dot 2H(2)O (2), [Co(L-3)Cl(H2O)(2)]center dot H2O (3) [Co(L-4)Cl(H2O)(2)]center dot H2O (4), [Co(L-5)Cl(H2O)(2)] center dot H2O (5) and [Co(L-6)Cl(H2O)(2)]center dot H2O (6), where HL1 = 6-(3-chlorobenzylamino)purine, HL2 = 6-(4-chlorobenzylamino)purine, HL3 = 6-(2,3-dimethoxybenzylamino)purine, HL4 = 6-(3,4-dimethoxybenzylamino)purine. HL5 = 6-(3-fluorobenzylamino)purine and HL6 = 6-(4-fluorobenzylamino)purine, have been prepared. The compounds have been characterized by elemental analyses, ES+ mass, UN-Vis, IR and NMR spectroscopies, magnetic measurements, molar conductances and thermogravimetric analysis as mononuclear tetrahedral high-spin cobalt(II) complexes. In vitro cytotoxicities of the complexes were tested by a Calcein AM assay against the following human tumour cell lines: malignant melanoma (G361), chronic myelogenous erythroleukemia, (K562), osteogenic sarcoma (HOS) and breast adenocarcinoma (MCF7). The molecular structures of 6-(4-chlorobenzylamino)purin-di-ium diperchlorate dihydrate, [H2+ L-2](ClO4)(2) center dot 2H(2)O, and a hexanuclear Co(II) complex, [Co-6(mu-L-6)(4)Cl-8(DMSO)(10)]center dot 4DMSO (7). have been determined by a single crystal X-ray analysis. To elucidate the manner of the organic ligand coordination to cobalt, the geometry of the complex 2 was optimized Using DFT calculations at the B3LYP/6-311+G* level of the theory. (c) 2005 Elsevier Ltd. All rights reserved., DOI = 10.1016/j.poly.2005.09.032, ISSN = 0277-5387, Unique-ID = ISI:000236698900022, - Z. Travnicek, J. Marek, and I. Popa, "6-(2-Chloro-4-fluorobenzylamino)purine," ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE, vol. 62, iss. Part 4, pp. O1536-O1538, 2006.
[Bibtex]@article ISI:000236470100255, Author = Travnicek, Z and Marek, J and Popa, I, Title = 6-(2-Chloro-4-fluorobenzylamino)purine, Journal = ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE, Year = 2006, Volume = 62, Number = Part 4, Pages = O1536-O1538, Month = APR, Abstract = In the title molecule, C12H9ClFN5, all bond lengths and angles show normal values. The mean planes of the benzene ring and the purine ring system make a dihedral angle of 77.79 (5)degrees. Intermolecular N - H (. . .) N hydrogen bonds link the molecules into ribbons extending along the [110] direction. The crystal packing is further stablized by weak C - H (. . .) F and C - H (. . .) Cl interactions., DOI = 10.1107/S1600536806009895, ISSN = 1600-5368, Unique-ID = ISI:000236470100255, - K. Dolezal, I. Popa, V. Krystof, L. Spichal, M. Fojtikova, J. Holub, R. Lenobel, T. Schmulling, and M. Strnad, "Preparation and biological activity of 6-benzylaminopurine derivatives
in plants and human cancer cells," BIOORGANIC & MEDICINAL CHEMISTRY, vol. 14, iss. 3, pp. 875-884, 2006.
[Bibtex]@article ISI:000234091700026, Author = Dolezal, K and Popa, I and Krystof, V and Spichal, L and Fojtikova, M and Holub, J and Lenobel, R and Schmulling, T and Strnad, M, Title = Preparation and biological activity of 6-benzylaminopurine derivatives in plants and human cancer cells, Journal = BIOORGANIC \& MEDICINAL CHEMISTRY, Year = 2006, Volume = 14, Number = 3, Pages = 875-884, Month = FEB 1, Abstract = To study the structure-activity relationships of aromatic cytokinins, the cytokinin activity at both the receptor and cellular levels, as well as CDK inhibitory and anticancer properties of 38 6-benzylaminopurine (BAP) derivatives were compared in various in vitro assays. The compounds were prepared by the condensation of 6-chloropurine with corresponding substituted benzylamines. The majority of synthesised derivatives exhibited high activity in all three of the cytokinin bioassays employed (tobacco callus, wheat senescence and Amaranthus bioassay). The highest activities were obtained in the senescence bioassay. For some compounds tested, significant differences of activity were found in the bioassays used, indicating that diverse recognition systems may operate and suggesting that it may be possible to modulate particular cytokinin-dependent processes with specific compounds. Position-specific steric and hydrophobic effects of different phenyl ring substituents on the variation of biological activity were confirmed. In contrast to their high activity in bioassays, the BAP derivatives were recognised with much lower sensitivity than trans-zeatin in both Arabidopsis thaliana AHK3 and AHK4 receptor assays. The compounds were also investigated for their effects on cyclin-dependent kinase 2 (CDK2) and for antiproliferative properties on cancer and normal cell lines. Several of the tested compounds showed stronger inhibitory activity and cytotoxicity than BAP. There was also a significant positive correlation of the inhibitory effects on human and plant CDKs with cell proliferation of cancer and cytokinin-dependent tobacco cells, respectively. This suggests that at least a part of the antiproliferative effect of the new cytokinins was due to the inhibition of CDK activity. (c) 2005 Elsevier Ltd. All rights reserved., DOI = 10.1016/j.bmc.2005.09.004, ISSN = 0968-0896, Unique-ID = ISI:000234091700026, - L. Szucova, Z. Travnicek, M. Zatloukal, and I. Popa, "Novel platinum(II) and palladium(II) complexes with cyclin-dependent
kinase inhibitors: Synthesis, characterization and antitumour activity," BIOORGANIC & MEDICINAL CHEMISTRY, vol. 14, iss. 2, pp. 479-491, 2006.
[Bibtex]@article ISI:000234091500019, Author = Szucova, L and Travnicek, Z and Zatloukal, M and Popa, I, Title = Novel platinum(II) and palladium(II) complexes with cyclin-dependent kinase inhibitors: Synthesis, characterization and antitumour activity, Journal = BIOORGANIC \& MEDICINAL CHEMISTRY, Year = 2006, Volume = 14, Number = 2, Pages = 479-491, Month = JAN 15, Abstract = The Pt(H) and Pd(II) complexes of the types cis-[Pt(L-1)(2)Cl-2]center dot H2O (1), cis-[Pt(L-2)(2)Cl-2]center dot 3H(2)O (2), trans- [Pd(L-1)(2)Cl-2]center dot H2O (3), trans-[Pd(L2)(2)Cl-2]center dot H2O (4), trans-[Pd(L-3)(2)Cl-2]2DMF (5) and trans-[Pd(L-4)(2)Cl-2]2DMF (6) (L-1-L-4 = cyclin-dependent kinase inhibitors derived from 6-benzylamino-9-isopropylpurine) have been prepared and characterized. The complexes have been studied by elemental analyses, conductivity measurements, ES+ MS, FT-IR, H, C-13 and Pt-195 NMR spectra, differential scanning calorimetry and thermogravimetric analysis. The molecular structures of L-1, trans-[Pd(L-3)(2)Cl-2](.)2DMF (5) and trans- [Pd(L-4)(2)Cl-2](.)2DMF (6) have been determined by single crystal X-ray analysis. The complexes have been tested in vitro due to their presumable anticancer activity against the following human cancer cell lines: K-562, MCF7, G-361 and HOS. Satisfying results were obtained for the complex 1 with IC50 values of 6 mu M acquired against G-361 as well as against HOS cell lines. The lowest values of IC50 were achieved for the complexes 3 and 4 against MCF 7 cell line with IC50 3 mu M (for 3) and also 3 mu M (for 4). (c) 2005 Elsevier Ltd. All rights reserved., DOI = 10.1016/j.bmc.2005.08.033, ISSN = 0968-0896, Unique-ID = ISI:000234091500019,
2005
- E. Hauserova, J. Swaczynova, K. Dolezal, R. Lenobel, I. Popa, M. Hajduch, D. Vydra, K. Fuksova, and M. Strnad, "Batch immunoextraction method for efficient purification of aromatic
cytokinins," JOURNAL OF CHROMATOGRAPHY A, vol. 1100, iss. 1, pp. 116-125, 2005.
[Bibtex]@article ISI:000234158600015, Author = Hauserova, E and Swaczynova, J and Dolezal, K and Lenobel, R and Popa, I and Hajduch, M and Vydra, D and Fuksova, K and Strnad, M, Title = Batch immunoextraction method for efficient purification of aromatic cytokinins, Journal = JOURNAL OF CHROMATOGRAPHY A, Year = 2005, Volume = 1100, Number = 1, Pages = 116-125, Month = DEC 23, Abstract = A range of benzylaminopurines naturally occur in plants and exhibit high biological activity. Others have been synthesized, such as 6-(2-hydroxy-3-methoxybenzylamino)purine riboside (2OH3MeOBAPR), which has shown interesting anti-cancer activity under in vitro conditions. In order to study the biological activity of this interesting compound in more detail, a rapid and highly efficient method for its purification from complex samples (e.g. blood and plant extracts) is needed. Therefore, we prepared monoclonal antibodies against 2OH3MeOBAPR. The antibody had undetectable cross-reactivity with all natural isoprenoid cytokinins, but relatively high cross-reactivity with aromatic cytokinins as well as some synthetic di- and tri-substituted 6-benzylaminopurines and the corresponding ribosides. The antibody also showed strong responses and specificity in enzyme-linked immunoassays (ELISAs). In addition, it was used to prepare, for the first time, an immunoaffinity sorbent with high specificity and capacity for aromatic cytokinins. A batch immunoextraction method was then developed and optimized for the purification of 2OH3MeOBAPR from murine blood samples. The high efficacy and simplicity of this method (in off-line combination with HPLC-MS) for the isolation of target analytes from biological material is demonstrated in this study. (c) 2005 Elsevier B.V. All rights reserved., DOI = 10.1016/j.chroma.2005.09.020, ISSN = 0021-9673, Unique-ID = ISI:000234158600015, - Z. Travnicek, M. Sipl, and I. Popa, "Palladium(II) complexes containing cytokinins derived from
6-benzylaminopurine," JOURNAL OF COORDINATION CHEMISTRY, vol. 58, iss. 16, pp. 1513-1521, 2005.
[Bibtex]@article ISI:000233020800015, Author = Travnicek, Z and Sipl, M and Popa, I, Title = Palladium(II) complexes containing cytokinins derived from 6-benzylaminopurine, Journal = JOURNAL OF COORDINATION CHEMISTRY, Year = 2005, Volume = 58, Number = 16, Pages = 1513-1521, Month = NOV 10, Abstract = A series of palladium(II) complexes of general formula [Pd(LH+)Cl-3] (1-12) containing 6-benzylaminopurine derivatives has been prepared [L=6-(2-methoxybenzylamino) purine (1), 6-(3-methoxybenzylamino)purine (2), 6-(4-methoxybenzylamino) purine (3), 6-(2-hydroxybenzylamino) purine (4), 6-(3-hydroxybenzylamino)purine (5), 6-(4-hydroxybenzylamino)purine (6), 6-(2-fluorobenzylamino)purine (7), 6-(3-fluorobenzylamino)purine (8), 6-(4-fluorobenzylamino)purine (9), 6-(2-chlorobenzylamino)purine (10), 6-(3-chlorobenzylamino)purine (11) and 6-(4-chlorobenzylamino)purine (12)]. The compounds have been characterized by elemental analysis, IR, ES+ MS and H-1- and C-13-NMR spectroscopy, and two of them, 6 and 12, also by TG/DSC analyses. The complexes have been screened in vitro against the four human tumour cell lines G-361, HOS, K-562 and MCF7., DOI = 10.1080/00958970500258898, ISSN = 0095-8972, Unique-ID = ISI:000233020800015, - Z. Travnicek, A. Klanicova, I. Popa, and J. Rolcik, "Synthetic, spectral, magnetic and in vitro cytotoxic activity studies of
cobalt(II) complexes with cytokinin derivatives: X-ray structure of
6-(3-methoxybenzylamino)purinium chloride monohydrate," JOURNAL OF INORGANIC BIOCHEMISTRY, vol. 99, iss. 3, pp. 776-786, 2005.
[Bibtex]@article ISI:000227374900013, Author = Travnicek, Z and Klanicova, A and Popa, I and Rolcik, J, Title = Synthetic, spectral, magnetic and in vitro cytotoxic activity studies of cobalt(II) complexes with cytokinin derivatives: X-ray structure of 6-(3-methoxybenzylamino)purinium chloride monohydrate, Journal = JOURNAL OF INORGANIC BIOCHEMISTRY, Year = 2005, Volume = 99, Number = 3, Pages = 776-786, Month = MAR, Abstract = Cobalt(II) complexes with 6-(2-hydroxybenzylamino)purine (HL1), 6-(2-methoxybenzylamino)purine (HL2), 6-(3-methoxybenzylamino)purine (HL3) and 6-(4-methoxybenzylamino)purine (HL4) of the composition [Co(L-1)Cl(H2O)(2)] (.) H2O (1), [Co(L-2)Cl(H2O)(2)] (2), [Co(L-3)(2)(H2O)(2)] (.) 2H(2)O (3), [Co(L-4)(2)(H2O)(2)] (.) 2H(2)O (4) have been synthesized. The compounds have been characterized by elemental analysis, FT-IR, ES + MS (electrospray mass spectra in the positive ion mode) and electronic spectroscopies, magnetic and conductivity data as tetrahedral high-spin cobalt(II) complexes. The thermal stability of the complexes has also been studied. The cytotoxicity of the complexes (1-4) was determined by a Calcein acetoxymethyl (AM) assay. Human malignant melanoma (G361), human chronic myelogenous erythroleukemia (K562), human osteogenic sarcoma (HOS) and human breast adenocarcinoma (MCF7) cell lines were used for the testing. The molecular structure of 6-(3-methoxybenzylamino)purinium chloride monohydrate, H2L3+ (.) Cl (.) H2O i.e. a protonated form of the free HL3 ligand, has been determined by a single crystal X-ray analysis. The geometry optimisation and infrared frequencies calculations of HL1, HL2, and H2L3+ and H2L4+ were performed using density-functional theory (DFT) calculations at the B3LYP/6-31G* level of the theory. The geometry of complex (1) was optimised at the same level of the theory. (C) 2004 Elsevier Inc. All rights reserved., DOI = 10.1016/j.jinorgbio.2004.12.002, ISSN = 0162-0134, Unique-ID = ISI:000227374900013,
2004
- Z. Travnicek, I. Popa, and K. Dolezal, "6-(4-methoxybenzylamino)purin-3-ium chloride," ACTA CRYSTALLOGRAPHICA SECTION C-CRYSTAL STRUCTURE COMMUNICATIONS, vol. 60, iss. Part 9, pp. O662-O664, 2004.
[Bibtex]@article ISI:000224226700035, Author = Travnicek, Z and Popa, I and Dolezal, K, Title = 6-(4-methoxybenzylamino)purin-3-ium chloride, Journal = ACTA CRYSTALLOGRAPHICA SECTION C-CRYSTAL STRUCTURE COMMUNICATIONS, Year = 2004, Volume = 60, Number = Part 9, Pages = O662-O664, Month = SEP, Abstract = The title compound, C13H14N5O+.Cl-, belongs to the group of aromatic cytokinins. These compounds affect a variety of important physiological processes in plants and animals as well as in bacteria, including cell division, differentiation and senescence. The structure consists of a 6-(4-methoxybenzylamino)purinium cation and a Cl. anion. The cation moiety exists as the N3-protonated N7 tautomer. The cation contains nearly planar benzene and purine ring systems, with a dihedral angle of 77.46 (5)degrees. The crystal structure is stabilized by N-amino-H...N-purine hydrogen bonds connecting two adjacent molecules, thus forming centrosymmetric dimers., DOI = 10.1107/S0108270104016749, ISSN = 0108-2701, Unique-ID = ISI:000224226700035,
2002
- Z. Travnicek, M. Malon, I. Popa, K. Dolezal, and M. Strnad, "Preparation and cytotoxic activity of nickel(II) complexes with
6-benzylaminopurine derivatives," TRANSITION METAL CHEMISTRY, vol. 27, iss. 8, pp. 918-923, 2002.
[Bibtex]@article ISI:000179572700019, Author = Travnicek, Z and Malon, M and Popa, I and Dolezal, K and Strnad, M, Title = Preparation and cytotoxic activity of nickel(II) complexes with 6-benzylaminopurine derivatives, Journal = TRANSITION METAL CHEMISTRY, Year = 2002, Volume = 27, Number = 8, Pages = 918-923, Month = NOV, Abstract = Nickel(II) complexes with 6-benzylaminopurine (BAP) derivatives, namely 6-(3-chlorobenzylamino) purine (HL1), 6-4-chlorobenzylamino) purine (HL2) and 6-(4-fluorobenzylamino) purine (HL3), have been prepared and characterized by elemental analyses, i.r., u.v.-v.i.s., ES+ and FAB+ mass spectroscopy, magnetic susceptibility and conductivity measurements, and by thermal analysis. The complexes are: [Ni(L-1(H2O)(2)Cl].H2O, [Ni(L-1)(H2O)(NO3)].H2O, [Ni(L-2)(H2O)(2)Cl], [Ni(L-2)(H2O)(2)(NO3)].H2O, [Ni(HL2)(H2O)Cl-2].EtOH and [Ni(L-3)(H2O)(2)Cl]. They have been tested in vitro for their possible cytotoxic activity against G-361 ( human malignant melanoma), HOS (human osteogenic sarcoma), K-562 (human chronic myelogenous leukemia) and MCF-7 ( human breast adenocarcinoma) cell lines., DOI = 10.1023/A:1021385217317, ISSN = 0340-4285, Unique-ID = ISI:000179572700019,