Email: pavel.starha@upol.cz
Location: 17. listopadu 12, Olomouc
Phone: (+420) 58 563 4346
Fax: (+420) 58 563 4357
Research activities:
Coordination chemistry
Transition metal (Pt, Pd, Cu etc.) complexes
Thermal analysis (TG, DTA, DSC) and isothermal titration calorimetry (ITC)
Biological (cytotoxic, antiradical etc.) activity of transition metal complexes
Qualification:
Mgr.: Education of biology and chemistry, Palacký University
Ph.D.: Inorganic chemistry, Palacký University
Publications
2011
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![[DOI]](http://www.rcptm.com/wp-content/plugins/papercite/img/external.png)
R. Pastorek, P. Starha, T. Peterek, and Z. Travnicek, “Nickel(IV) dithiocarbamato complexes of the [Ni(ndtc)(3)]X type: X-ray
structure of [Ni(hmidtc)(3)][FeCl(4)],” POLYHEDRON, vol. 30, iss. 17, pp. 2795-2800, 2011.
[Bibtex]@article ISI:000296996500006, Author = Pastorek, Richard and Starha, Pavel and Peterek, Tomas and Travnicek, Zdenek, Title = Nickel(IV) dithiocarbamato complexes of the [Ni(ndtc)(3)]X type: X-ray structure of [Ni(hmidtc)(3)][FeCl(4)], Journal = POLYHEDRON, Year = 2011, Volume = 30, Number = 17, Pages = 2795-2800, Month = NOV 3, Abstract = A series of fourteen octahedral nickel(IV) dithiocarbamato complexes of the general formula \Ni(ndtc)(3)]X center dot yH(2)O \ndtc stands for the appropriate dithiocarbamate anion, X stands for ClO(4)(-) (1-8; y = 0) or [FeCl(4)](-) (9-14; y = 0 for 9-12, 1 for 13 and 0.5 for 14) was prepared by the oxidation of the corresponding nickel(II) complexes, i.e. [Ni(ndtc)(2)], with NOClO(4) or FeCl(3). The complexes, involving a high-valent Ni(IV)S(6) core, were characterized by elemental analysis (C, H, N. Cl and Ni), UV-Vis and FTIR spectroscopy, thermal analysis and magnetochemical and conductivity measurements. The X-ray structure of \Ni(hmidtc)(3)][FeCl(4)] (9) was determined \it consists of covalently discrete complex [Ni(hmidtc)(3)](+) cations and [FeCl(4)](-) anions\ and this revealed slightly distorted octahedral and tetrahedral geometries within the complex cations, and anions, respectively. The Ni(IV) atom is six-coordinated by three bidentate S-donor hexamethyleneiminedithiocarbamate anions (hmidtc), with Ni-S bond lengths ranging from 2.2597(5) to 2.2652(5)angstrom, while the shortest Ni center dot center dot center dot Cl and Ni center dot center dot center dot Fe distances equal 4.1043(12), and 6.2862(6) angstrom, respectively. Moreover, the formal oxidation state of iron in (FeCl(4)](-) as well as the coordination geometry in its vicinity was also proved by (57)Fe Mossbauer spectroscopy in the case of 9. (C) 2011 Elsevier Ltd. All rights reserved., DOI = 10.1016/j.poly.2011.08.022, ISSN = 0277-5387, Unique-ID = ISI:000296996500006, - R. Pastorek, Z. Travnicek, and P. Starha, “Octahedral nickel(II) hexamethyleneimine-dithiocarbamato complexes
involving bidentate N,N-donor ligands,” INORGANICA CHIMICA ACTA, vol. 373, iss. 1, pp. 286-290, 2011.
[Bibtex]@article ISI:000291244600042, Author = Pastorek, Richard and Travnicek, Zdenek and Starha, Pavel, Title = Octahedral nickel(II) hexamethyleneimine-dithiocarbamato complexes involving bidentate N,N-donor ligands, Journal = INORGANICA CHIMICA ACTA, Year = 2011, Volume = 373, Number = 1, Pages = 286-290, Month = JUL 15, Abstract = The nickel(II) complexes of the compositions [Ni(hmidtc)(bpy)(2)]ClO(4) (I), [Ni(hmidtc)(phen)(2)] ClO(4) (II), [Ni(hmidtc)(phen)(2)] SCN (III), [Ni(hmidtc)(phen)(2)]PF(6) (IV), [Ni(hmidtc)(phen)(2)]BPh(4) (V), [Ni(hmidtc) (phen)(2)]AcO center dot 2H(2)O (VI) and [Ni(hmidtc)(phen)(2)]Br center dot H(2)O (VII), involving a combination of one hexamethyleneimine-dithiocarbamate anion (hmidtc) and two bidentate N, N-donor ligands (2,2'-bipyridine (bpy) for I or 1,10-phenanthroline (phen) for II-VII), have been prepared. The compounds were characterized by elemental analysis, molar conductivity measurements, UV-Vis and IR spectroscopy, magnetochemical measurements and thermal analysis. A single-crystal X-ray analysis of the complex I revealed a distorted octahedral geometry with the nickel(II) ion coordinated by four nitrogen atoms (from two bidentate-coordinated bpy molecules) and two sulfur atoms (from one bidentate-coordinated hmidtc anion), together giving an NiN(4)S(2) donor set. (C) 2011 Elsevier B. V. All rights reserved., DOI = 10.1016/j.ica.2011.03.010, ISSN = 0020-1693, Unique-ID = ISI:000291244600042, - Z. Dvorak, P. Starha, and Z. Travnicek, “Evaluation of in vitro cytotoxicity of 6-benzylaminopurine carboplatin
derivatives against human cancer cell lines and primary human
hepatocytes,” TOXICOLOGY IN VITRO, vol. 25, iss. 3, pp. 652-656, 2011.
[Bibtex]@article ISI:000288933100008, Author = Dvorak, Zdenek and Starha, Pavel and Travnicek, Zdenek, Title = Evaluation of in vitro cytotoxicity of 6-benzylaminopurine carboplatin derivatives against human cancer cell lines and primary human hepatocytes, Journal = TOXICOLOGY IN VITRO, Year = 2011, Volume = 25, Number = 3, Pages = 652-656, Month = APR, Abstract = A series of seven platinum(II) cyclobutane-1,1-dicarboxylato (cbdc) complexes \[Pt(cbdc)(L(n))(2)], 1-7\, derived from carboplatin by a substitution of two NH(3) molecules for two 2,6,9-trisubstituted 6-benzyl-aminopurinc-based N-donor ligands (L(n)), was studied by the MTT assay for their in vitro cytotoxic activity against seven human cancer cell lines, i.e. lung carcinoma (A549), cervix epithelioid carcinoma (HeLa), osteosarcoma (HOS), malignant melanoma (G361), breast adenocarcinoma (MCP), ovarian carcinoma (A2780) and its cisplatin-resistant analogue (A2780cis), and against two primary cultures of human hepatocytes (LH31 and LH32). The prepared complexes were cytotoxic against several cancer cells, in some cases even more than cisplatin. The best results were achieved for complexes 1 (IC(50) = 17.4 +/- 2.0 mu M) and 2 (IC(50) = 14.8 +/- 2.1 mu M) against HOS cells, 1 (IC(50) = 15.1 +/- 6.8 mu M), 2 (IC(50) = 13.6 +/- 5.2 mu M) and 6 (IC(50) = 19.0 +/- 6.6 mu M) against MCF7, 6 (IC(50) = 6.4 +/- 0.1 mu M) against A2780, and 1-6 (IC(50) = 15.6 +/- 4.0, 12.9 +/- 3.7, 15.8 +/- 3.8, 16.6 +/- 5.5, 22.1 +/- 2.5, and 5.6 +/- 1.7 mu M, respectively) against A2780cis. Viability of human hepatocytes was not declined by the tested complexes up to the concentration of 50 mu M (for 1, 3-7) and 20 mu M (for 2; caused by lower solubility of this complex). (c) 2011 Elsevier Ltd. All rights reserved., DOI = 10.1016/j.tiv.2011.01.002, ISSN = 0887-2333, Unique-ID = ISI:000288933100008,
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, - R. Vrzal, P. Starha, Z. Dvorak, and Z. Travnicek, “Evaluation of in vitro cytotoxicity and hepatotoxicity of platinum(II)
and palladium(II) oxalato complexes with adenine derivatives as carrier
ligands,” JOURNAL OF INORGANIC BIOCHEMISTRY, vol. 104, iss. 10, pp. 1130-1132, 2010.
[Bibtex]@article ISI:000281525200017, Author = Vrzal, Radim and Starha, Pavel and Dvorak, Zdenek and Travnicek, Zdenek, Title = Evaluation of in vitro cytotoxicity and hepatotoxicity of platinum(II) and palladium(II) oxalato complexes with adenine derivatives as carrier ligands, Journal = JOURNAL OF INORGANIC BIOCHEMISTRY, Year = 2010, Volume = 104, Number = 10, Pages = 1130-1132, Month = OCT, Abstract = In vitro antitumour activity of the [Pt(ox)(L(n))(2)] (1-7) and [Pd(ox)(L(n))(2)] (8-14) oxalato (ox) complexes involving N6-benzyl-9-isopropyladenine-based N-donor carrier ligands (L(n)) 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 studied. Some of the tested complexes were even several times more cytotoxic as compared with cisplatin employed as a positive control. The improved cytotoxic effect was demonstrated for the platinum(II) complexes 3 (IC(50) = 3.2 +/- 1.0 mu M and 3.2 +/- 0.6 mu M) and 5 (IC(50) = 4.0 +/- 1.0 mu M and 4.1 +/- 1.4 mu M) against A2780 and A2780cis, as compared with 11.5 +/- 1.6 mu M, and 30.3 +/- 6.1 mu M determined for cisplatin, respectively. The significant in vitro cytotoxicity against MCF7 (IC(50) = 8.2 +/- 3.8 mu M for 12) and A2780 (IC(50) = 5.4 +/- 1.2 mu M for 14) was evaluated for the palladium(II) oxalato complexes, which again exceeded cisplatin, whose IC(50) equalled 19.6 +/- 4.3 mu M against the MCF7 cells. Selected complexes were also screened for their in vitro cytotoxic effect in primary cultures of human hepatocytes and they were found to be non-hepatotoxic. (c) 2010 Elsevier Inc. All rights reserved., DOI = 10.1016/j.jinorgbio.2010.07.002, ISSN = 0162-0134, Unique-ID = ISI:000281525200017, - 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, - P. Starha, R. Novotna, and Z. Travnicek, “X-ray structure and properties of a dinuclear palladium(II) complex
[Pd(2)(mu-L)(4)] with four adenine-based bridges in a paddle
wheel-like arrangement,” INORGANIC CHEMISTRY COMMUNICATIONS, vol. 13, iss. 6, pp. 800-803, 2010.
[Bibtex]@article ISI:000279136700029, Author = Starha, Pavel and Novotna, Radka and Travnicek, Zdenek, Title = X-ray structure and properties of a dinuclear palladium(II) complex [Pd(2)(mu-L)(4)] with four adenine-based bridges in a paddle wheel-like arrangement, Journal = INORGANIC CHEMISTRY COMMUNICATIONS, Year = 2010, Volume = 13, Number = 6, Pages = 800-803, Month = JUN, Abstract = A unique dinuclear palladium(II) complex of the general composition [Pd(2)(mu-L)(4)]center dot xDMF (DMF = N,N'-dimethylformamide, x=2 for la, x = 4 for 1b) was prepared by a reaction of K(2)[Pd(mal)(2)] and two molar equivalents of 2-chloro-N6-benzyl-9-isopropyladenine (HL); mal stands for the malonate dianion. The prepared complex was fully characterized by elemental analysis, molar conductivity measurements, IR. Raman and NMR spectroscopies, ESI + mass spectrometry, TG/DTA thermal studies (for la), and by a single crystal X-ray analysis (for 1b). The results revealed that both metal centres are bridged by four N6-deprotonated2-chloro-N6-benzyl-9-isopropyladenine molecules (L) in a paddle wheel-like arrangement with the Pd1 ... Pd1A separation of 2.7532(4) angstrom. Each of the L molecules is coordinated to the Pd(II) ions through its N6 and N7 atoms. The geometry around each of the central atoms can be described as distorted square-planar formed by two N6 and two N7 atoms. The [Pd(2)(mu-L)(4)]center dot xDMF complex represents the first dinuclear transition metal complex with two central ions bridged by four adenine derivatives coordinated through their N6 and N7 atoms. (C) 2010 Elsevier By. All rights reserved., DOI = 10.1016/j.inoche.2010.04.001, ISSN = 1387-7003, Unique-ID = ISI:000279136700029, - 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, - 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. Dvorak, R. Vrzal, P. Starha, A. Klanicova, and Z. Travnicek, “Effects of dinuclear copper(II) complexes with 6-(benzylamino)purine
derivatives on AhR and PXR dependent expression of cytochromes P450
CYP1A2 and CYP3A4 genes in primary cultures of human hepatocytes,” TOXICOLOGY IN VITRO, vol. 24, iss. 2, pp. 425-429, 2010.
[Bibtex]@article ISI:000275991700011, Author = Dvorak, Zdenek and Vrzal, Radim and Starha, Pavel and Klanicova, Alena and Travnicek, Zdenek, Title = Effects of dinuclear copper(II) complexes with 6-(benzylamino)purine derivatives on AhR and PXR dependent expression of cytochromes P450 CYP1A2 and CYP3A4 genes in primary cultures of human hepatocytes, Journal = TOXICOLOGY IN VITRO, Year = 2010, Volume = 24, Number = 2, Pages = 425-429, Month = MAR, Abstract = A series of dinuclear copper(II) complexes of the compositions [Cu(2)(mu-L(n))(2)(mu-Cl)(2)Cl(2)] (1, 2), [Cu(2)(mu-L(n))(4)Cl(2)]Cl(2)center dot 2H(2)O (3, 4) and [Cu(2)(mu-L(n))(4)(ClO(4))(2)](ClO(4))(2)center dot xSolv (5, 6; xSolv = 4MeOH for 5 and 2EtOH for 6), involving 6-(benzylamino)purine derivatives (L(n)), have been evaluated with the aim to determine their possible drug interactions and their capability to induce the expression of major drug-metabolizing cytochromes P450. The above-mentioned complexes have been chosen based on the fact that substantial both in vitro (cytotoxicity, SOD-mimic) and in vivo (antidiabetic) biological activity has been found for them. As models, primary cultures of human hepatocytes and human hepatoma cells HepG2 transiently transfected with a plasmid containing dioxin-responsive element fused to the luciferase reporter gene (DRE-LUC) have been chosen. It has been found that the tested complexes 1-6 did not significantly induce the expression of CYP1A2 and CYP3A4 mRNAs in the concentration range of 0.1-10.0 mu M, in three different primary human hepatocyte cultures after 24 h of the treatment. On the other hand, the model inducers, i.e. 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) and rifampicin, significantly increased the levels of CYP1A2 and CYP3A4 mRNAs in all cultures. In addition, compounds 1-6 did not transactivate DRE-LUC in transiently transfected HepG2, while TCDD strongly induced luciferase activity after 24 h of incubation. Based on the obtained results, it may be concluded that the studied dinuclear copper(II) complexes 1-6 possess very low toxicological potential to cause drug interactions in terms of transcriptional activation of the major human cytochromes P450. (C) 2009 Elsevier Ltd. All rights reserved., DOI = 10.1016/j.tiv.2009.10.012, ISSN = 0887-2333, Unique-ID = ISI:000275991700011, - 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
- 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, - 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,