Flavone-based dual PARP-Tubulin inhibitor manifesting efficacy against endometrial cancer

Structural tailoring of the flavone framework (position 7) via organopalladium-catalyzed C-C bond formation was attempted in this study. The impact of substituents with varied electronic effects (phenyl ring, position 2 of the benzopyran scaffold) on the antitumor properties was also assessed. Resultantly, the efforts yielded a furyl arm bearing benzopyran possessing a 4-fluoro phenyl ring (position 2) (14) that manifested a magnificent antitumor profile against the Ishikawa cell lines mediated through dual inhibition of PARP and tubulin [(IC₅₀ (PARP1) = 74 nM, IC₅₀ (PARP2) = 109 nM) and tubulin (IC₅₀ = 1.4 µM)]. Further investigations confirmed the ability of 14 to induce Apoptosis as well as Autophagy and cause cell cycle arrest at the G2/M phase. Overall, the outcome of the study culminated in a tractable dual PARP-tubulin inhibitor endowed with an impressive activity profile against endometrial Cancer.

Flavone; PARP; benzopyran; endometrial cancer; inhibitor; tubulin.