20.500.12556/RUL-135447 Organoruthenium complexes with benzo-fused pyrithiones overcome platinum resistance in ovarian cancer cells Drug resistance to existing anticancer agents is a growing clinical concern, with many first line treatments showing poor efficacy in treatment plans of some cancers. Resistance to platinum agents, such as cisplatin, is particularly prevalent in the treatment of ovarian cancer, one of the most common cancers amongst women in the developing world. Therefore, there is an urgent need to develop next generation of anticancer agents which can overcome resistance to existing therapies. We report a new series of organoruthenium(II) complexes bearing structurally modified pyrithione ligands with extended aromatic scaffold, which overcome platinum and adriamycin resistance in human ovarian cancer cells. The mechanism of action of such complexes appears to be unique from that of cisplatin, involving G$_1$ cell cycle arrest without generation of cellular ROS, as is typically associated with similar ruthenium complexes. The complexes inhibit the enzyme thioredoxin reductase (TrxR) in a model system and reduce cell motility towards wound healing. Importantly, this work highlights further development in our understanding of the multi-targeting mechanism of action exhibited by transition metal complexes. ruthenium pyrithione resistance to chemotherapy cancer ovarian thioredoxin rutenij organorutenijevi kompleksi piritioni rak jajčnikov true false true Angleški jezik Slovenski jezik Članek v reviji 2022-03-15 12:24:34 2022-03-15 12:24:35 2022-09-14 04:13:22 0000-00-00 00:00:00 2021 0 0 21 str. iss. 10, art. 2493 Vol. 13 May 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 546.96:547.8:618.11-006 2072-6694 10.3390/cancers13102493 64129539 RAZ_Kladnik_Jerneja_2021.pdf RAZ_Kladnik_Jerneja_2021.pdf 1 C069A57EB65F60B7C01CC82570AAF965 9cca74a297ab63c8d3a6f1d2e7527b2f0eb4ac7288fa18e876842b2e89a48a2f d8711231-a452-11ec-8556-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=154534 https://www.mdpi.com/2072-6694/13/10/2493 0 7d0c8892-a452-11ec-8556-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=154533 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0