ABSTRACT
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.
Subject(s)
Antineoplastic Agents , Endometrial Neoplasms , Flavones , Humans , Female , Tubulin Modulators/pharmacology , Tubulin Modulators/chemistry , Tubulin/metabolism , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Cell Line, Tumor , Drug Screening Assays, Antitumor , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Apoptosis , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/pathology , Flavones/pharmacology , Benzopyrans , Cell ProliferationABSTRACT
Foreign body in the oral cavity can be encountered by Head and Neck Surgeons in their clinical practice. Here, we report a rare case of an embedded sewing machine needle in the posterior tongue that migrated by tongue movements, and was retrieved successfully by surgical intervention.
