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

AbstractStructural 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

Unveiling the healing properties of 2,3-dehydrosilychristin: a potential silymarin-derived flavonolignan from <i>Vitex negundo</i>

The compound 2,3-dehydrosilychristin, a flavonolignan linked to silychristin and silymarin, remains intriguing due to its challenging isolation from silymarin. While silymarin has been the exclusive source of flavonolignans – silybin, silychristin and silydianin − 2,3-dehydrosilychristin is reported in this study from Vitex negundo Linn. leaves. 2,3-Dehydrosilychristin (7) and 14 other compounds were isolated through focused extraction. Its subsequent pharmacological evaluation demonstrated potent antioxidant and in-vitro anti-inflammatory effects, notably inhibiting cytokines TNF-α, IL-6, IL-8 and VEGF. In in-vivo assessments, 2,3-dehydrosilychristin (7) revealed remarkable hepatoprotective potential by reducing liver enzyme levels AST and ALT. These findings expand the potential of 2,3-dehydrosilychristin and suggest bioprospecting Vitex species as alternate sources of bioactive flavonolignans.</p