RESUMO
Regio-/stereoselective Michael addition to ring A of withaferin-A was performed using an optimized reaction procedure to synthesise a library of 2,3-dihydro,3-ß-substituted withaferin-A derivatives. The analogues thus obtained were evaluated for in vitro cytotoxicity against various human cancer cell lines. 3-Azido analogue exhibited 35-fold increase (IC(50)=0.02-1.9 µM) in cytotoxicity against almost the entire cell lines tested when compared to the parent molecule. However, further modifications of 3-azido analogue with various alkynes under Husigen's cycloaddition conditions generated a variety of triazole derivatives with reduced cytotoxicity.
Assuntos
Vitanolídeos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Relação Estrutura-Atividade , Triazóis/química , Triazóis/farmacologia , Vitanolídeos/isolamento & purificaçãoRESUMO
2-Aryl-4,5-bis(diphenyl)-1-(N-acetyl hydrazide)-1,3-imidazoline (IIb1-4) was prepared by the reaction of ethyl chloro acetate and hydrazine hydrate with 2-Aryl-4,5-bis (diphenyl)-1H-imidazoline (I a1-4), which on further substitution with aryl/heterocyclyl aldheyde gave 2-Aryl-4,5-bis (diphenyl)-1-(4-substituted hydrazone)-1,3-imidazoline (III Ca-i). This was again cyclised to oxadiazole in the presence of ferric chloride and glacial acetic acid yielded 2-Aryl-4,5-bis(diphenyl)-1-(2-substituted-1,3,4-oxadizole)-1,3-imi dazoline (IV da-i). These compounds were screened for hypotensive activity and an attempt were made to get the site of action of these compounds.
