RESUMO
Azadirone 1, a limonoidal constituent of Azadirachta indica is found to possess potent cytotoxic activity against a panel of human cancer cell lines in our in vitro studies. In vitro screening of a number of semi-synthetic analogues of 1 revealed that the alpha,beta-unsaturated enone moiety or its equivalent conjugated system in A-ring, C-7 acetyloxy/chloroacetyloxy or keto group in B-ring and the furan moiety are responsible for the activity of 1 and its analogues. Compound 1 and two of the semi-synthetic analogues 10 and 13 were found to possess good in vivo antitumor activity in modified hollow fiber animal models.
Assuntos
Antineoplásicos/química , Antineoplásicos/toxicidade , Azadirachta/química , Limoninas/toxicidade , Antineoplásicos/síntese química , Antineoplásicos/isolamento & purificação , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Limoninas/síntese química , Limoninas/isolamento & purificação , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Andrographolide 1, the cytotoxic agent of the plant Andrographis paniculata was subjected to semi-synthetic studies leading to the preparation of a number of potent and novel analogues. Of the analogues synthesized, while 8,17-epoxy andrographolide 6 retained the cytotoxic activity of 1, ester derivatives of 6 exhibited considerable improvement in activity. Lower activity was observed when the epoxy moiety in the triacetate 9, derived from 6 was modified. Synthesis and structure-activity relationships are discussed.