RESUMO
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.
Assuntos
Antineoplásicos , Neoplasias do Endométrio , Flavonas , Humanos , Feminino , Moduladores de Tubulina/farmacologia , Moduladores de Tubulina/química , Tubulina (Proteína)/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos/farmacologia , Antineoplásicos/química , Apoptose , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Flavonas/farmacologia , Benzopiranos , Proliferação de CélulasRESUMO
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.