Selectivity for TP53 signalling drives the mode of action of a highly potent <i>N</i>,<i>O</i>,<i>O</i>-tridentate naphthoquinone-based organo-ruthenium anticancer drug candidate.

ABSTRACT: The metallodrug candidate [(3-ethyl-4-oxo-(pyrazolyl)-dihydronaphthalene)(cymene)ruthenium(ii)] (1a) was recently shown to exhibit exceptional antiproliferative activity towards the chemo-resistant SW480 cancer cell line with nanomolar potency. This study was conducted to elucidate the determining parameters of the mode of action of this N,O,O-tridentate organoruthenium compound in vitro and in vivo. Four metal(arenes) based on 3-ethyl naphthoquinone (3-Et-NQ, a) and 3-morpholine naphthoquinone (3-Morph-NQ, b) with ruthenium (1) and osmium (2) were synthesized and characterized. The 3-Morph-NQ ligand increased the solubility of the complexes, but showed a 30-fold reduction in antiproliferative activity compared to the 3-Et-NQ ligand and its complexes serv

SUBMITTER: Rosner A 

PROVIDER: S-EPMC12320299 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature