Ru(III) Complexes with Lonidamine-Modified Ligands
Ilya A. Shutkov, Yulia N. Okulova, V. Yu. Tyurin, E. V. Sokolova, Denis A. Babkov, А. А. Спасов, Yulia A. Gracheva, Claudia Schmidt, К. I. Kirsanov, Аlexander А. Shtil, Olga Redkozubova, E. F. Shevtsova, Е. Р. Милаева, Ingo Ott, Alexey A. Nazarov
Abstract
A series of bifunctional Ru(III) complexes with lonidamine-modified ligands (lonidamine is a selective inhibitor of aerobic glycolysis in cancer cells) was described. Redox properties of Ru(III) complexes were characterized by cyclic voltammetry. An easy reduction suggested a perspective for these agents as their whole mechanism of action seems to be based on activation by metal atom reduction. New compounds demonstrated a more pronounced antiproliferative potency than the parental drug; individual new agents were more cytotoxic than cisplatin. Stability studies showed an increase in the stability of complexes along with the linker length. A similar trend was noted for antiproliferative activity, cellular uptake, apoptosis induction, and thioredoxin reductase inhibition. Finally, at concentrations that did not alter water solubility, the selected new complex evoked no acute toxicity in Balb/c mice.