RESUMO
A series of 4-(3'-indolyl)oxazole congeners have been synthesized and studied for their cytotoxicity against six cancer cell lines. Reaction of 3-acetyl-1'-benzenesulfonylindole with [hydroxy(tosyloxy)iodo]benzene afforded pure 3-tosyloxyacetyl-1'-benzenesulfonylindole. Microwave-accelerated neat reaction of 3-tosyloxyacetyl-1-benzenesulfonylindole with amides resulted in the exclusive formation of 4-(1'-benzenesulfonylindol-3'-yl)-2-substituted oxazoles (4) in very good yield. Treatment of 4 with aqueous sodium hydroxide under refluxing conditions afforded pure 4-(3'-indolyl)-2-substituted oxazoles (5) in excellent yield. The 4-(3'-indolyl)oxazoles 5d and 11 were found to be most cytotoxic and selective against various cancer cell lines. Compounds 5g, 5j and 5l showed moderate anticancer activity.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Indóis/síntese química , Indóis/farmacologia , Oxazóis/síntese química , Oxazóis/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Indóis/química , Estrutura Molecular , Neoplasias/tratamento farmacológicoRESUMO
A facile, convenient and high yielding synthesis of a series of novel 5-(3'-indolyl)-2-(substituted)-1,3,4-oxadiazoles from readily available starting materials has been described. The key step of this protocol is oxidative cyclization of N-acylhydrazones 1 using [bis(trifluoroacetoxy)iodo]benzene under solvent-free condition. The 5-(3'-indolyl)-2-(substituted)-1,3,4-oxadiazoles were screened for their in vitro anticancer activity against various human cancer cell lines. Compounds 3c, 3d and 3j exhibited potent cytotoxicity (IC(50) approximately 1microM) and selectivity against human cancer cell lines.
