Discovery of Potent Isoquinolinequinone N-Oxides to Overcome Cancer Multidrug Resistance.

ABSTRACT: Multidrug resistance (MDR) of human tumors has resulted in an immediate need to develop appropriate new drugs. This work outlines the development of 20 potent IQQ N-oxide derivatives in two isomeric families, both exhibiting nanomolar GI₅₀ against human tumor cell lines. Preliminary NCI-60 tumor screening sees the C(6) isomers achieve a mean GI₅₀ > 2 times lower than the corresponding C(7) isomers. MDR evaluation of nine selected compounds reveals that each presents lower GI₅₀ concentrations in two MDR tumor cell lines. Four of the series display nanomolar GI₅₀ values against MDR cells, having selectivity ratios up to 2.7 versus the sensitive (parental) cells. The most potent compound 25 inhibits the activity of drug efflux pumps in

SUBMITTER: Kruschel RD 

PROVIDER: S-EPMC11345829 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature