RESUMO
BACKGROUND: The 3,4-diyne substituted isocoumarins have been designed, synthesized and explored as potential anti-proliferative agents. METHOD: Ultrasound assisted synthesis of these compounds was carried out by using a three-step method involving (i) Pd/C-Cu catalyzed cross-coupling between the methyl 2-iodobenzoate and buta- 1,3-diynylbenzene followed by (ii) I2-mediated electrophilic cyclization of the resultant 2-(alk-1- ynyl)benzoate ester and (iii) subsequent alkynylation of 4-iodo-3-(phenylethynyl)-isocoumarin under Pd/C-Cu catalysis. CONCLUSION: The synthesized compounds showed promising growth inhibition when tested against MDA-MB 231 and K562 cancer cell lines.
Assuntos
Antineoplásicos/farmacologia , Citotoxinas/farmacologia , Di-Inos/farmacologia , Isocumarinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citotoxinas/síntese química , Citotoxinas/química , Di-Inos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Isocumarinas/síntese química , Isocumarinas/química , Relação Estrutura-AtividadeRESUMO
BACKGROUND: 3-Methyleneisoindolin-1-one derivatives containing a pyridin-2-ylmethyl substituent on their ring nitrogen were designed as potential bioactive agents. A one-pot synthesis of these compounds was achieved via sequential C-C coupling, followed by C-Si bond cleavage and subsequent tandem C-C/C-N bond forming reaction under ultrasound irradiation. METHOD: The methodology involved coupling of (trimethylsilyl)acetylene with iodoarenes in the presence of 10% Pd/C-CuI-PPh3-Et3N in MeOH followed by treating the reaction mixture with K2CO3 in aqueous MeOH, and finally coupling with 2-iodo-N-(pyridin-2-ylmethyl)benzamide. The in vitro evaluation of these compounds was performed to identify some initial hit molecules one of which showed dose dependent inhibition of PDE4B.
