Discovery of Halogenated Benzothiadiazine Derivatives with Anticancer Activity*.

ABSTRACT: Mitochondrial respiratory complex II (CII), also known as succinate dehydrogenase, plays a critical role in mitochondrial metabolism. Known but low potency CII inhibitors are selectively cytotoxic to cancer cells including the benzothiadiazine-based anti-hypoglycemic diazoxide. Herein, we study the structure-activity relationship of benzothiadiazine derivatives for CII inhibition and their effect on cancer cells for the first time. A 15-fold increase in CII inhibition was achieved over diazoxide, albeit with micromolar IC₅₀ values. Cytotoxicity evaluation of the novel derivatives resulted in the identification of compounds with much greater antineoplastic effect than diazoxide, the most potent of which possesses an IC₅₀ of 2.93±0.07 μM in a cellular model of triple-ne

SUBMITTER: Huwaimel BI 

PROVIDER: S-EPMC8035258 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature