Publication in Bioorganic Chemistry

New Glycoconjugation Strategies for Ruthenium(II) Arene Complexes via Phosphane Ligands and Assessment of their Antiproliferative Activity


Authors: Dalila Iacopini, Ján Vančo, Sebastiano Di Pietro, Vittorio Bordoni, Stefano Zacchini, Fabio Marchetti, Zdeněk Dvořák, Tomáš Malina, Lorenzo Biancalana, Zdeněk Trávníček, Valeria Di Bussolo



A series of ruthenium(II) p-cymene complexes derivatized with 2,3-unsaturated glycosides was prepared and characterized by our colleagues from University of Pisa and University of Bologna, Italy. The compounds were screened for their in vitro cytotoxicity against eight human cancer cell lines, revealing a significant cytotoxicity for complexes containing the 2,3-unsaturated glycosyl unit (Ru1β, Ru1α). Additional studies on time-dependent toxicity and cell-uptake analyses on ovarian cancer cells, confirmed the prominent activity of these two compounds – higher than cisplatin – and the better performance of the β anomer. However, Ru1β, Ru1α did not show preferential activity against cancer cells with respect to fetal lung fibroblast and human embryonic kidney cells as models of normal cells. The effects of the two ruthenium glycoconjugated compounds in A2780 ovarian cancer cells were further investigated by cell cycle analysis, induction of apoptosis, intracellular ROS production, activation of caspases 3/7 and disruption of mitochondrial membrane potential. The latter is a relevant factor in the mechanism of action of the highly cytotoxic Ru1β, inducing cell death by apoptosis.