20.500.12556/RUL-145365 Ruthenium complexes show potent inhibition of AKR1C1, AKR1C2, and AKR1C3 enzymes and anti-proliferative action against chemoresistant ovarian cancer cell line In this study, we present the synthesis, kinetic studies of inhibitory activity toward aldo-keto reductase 1C (AKR1C) enzymes, and anticancer potential toward chemoresistant ovarian cancer of 10 organoruthenium compounds bearing diketonate (1–6) and hydroxyquinolinate (7–10) chelating ligands with the general formula [(η$^6$-p-cymene)Ru(chel)(X)]$^{n+}$ where chel represents the chelating ligand and X the chlorido or pta ligand. Our studies show that these compounds are potent inhibitors of the AKR enzymes with an uncommon inhibitory mechanism, where two inhibitor molecules bind to the enzyme in a first fast and reversible step and a second slower and irreversible step. The binding potency of each step is dependent on the chemical structure of the monodentate ligands in the metalloinhibitors with the chlorido complexes generally acting as reversible inhibitors and pta complexes as irreversible inhibitors. Our study also shows that compounds 1–9 have a moderate yet better anti-proliferative and anti-migration action on the chemoresistant ovarian cancer cell line COV362 compared to carboplatin and similar effects to cisplatin. ruthenium complexes synthesis crystal structure anticancer aldo-keto reductase enzyme inhibition rutenijevi kompleksi sinteza kristalna struktura true false true Angleški jezik Slovenski jezik Članek v reviji 2023-04-19 10:37:19 2023-04-19 10:37:22 2023-04-20 03:39:12 0000-00-00 00:00:00 2022 0 0 15 str. Vol. 13, art. 920379 2022 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 618.1 1663-9812 10.3389/fphar.2022.920379 115794691 fphar-13-920379.pdf fphar-13-920379.pdf 1 13059C55BAB912588925086FA0DB8B0D ef513fdca220cbbbbcbcd36a80c16d597660270199d256ef90f312ba1f392bba 1fcca97f-de90-11ed-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=168241 https://www.frontiersin.org/articles/10.3389/fphar.2022.920379/full 0 f3fa30a3-de8f-11ed-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=168240 Fakulteta za kemijo in kemijsko tehnologijo Medicinska fakulteta 0 0 0