RESUMO
A series of novel indolizinophthalazine-5,12-dione derivatives were designed and synthesized by the reaction of 6,7-dichlorophthalazine-5,8-dione with active methylene reagents (AMR) and pyridine derivatives. Some of synthesized compounds exhibited significant in vitro antiproliferative activity at micromolar level toward four human tumor cell lines, including lung adenocarcinoma cell, large-cell lung carcinoma cell, breast carcinoma cell and ardriamycin-resistance breast carcinoma cell. The DNA topoisomerase IB inhibitory assay indicated that DNA topoisomerase IB might be a biological target of the synthesized compounds.
Assuntos
DNA Topoisomerases Tipo I/metabolismo , Indolizinas/síntese química , Indolizinas/farmacologia , Ftalazinas/síntese química , Ftalazinas/farmacologia , Inibidores da Topoisomerase I/síntese química , Inibidores da Topoisomerase I/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenho de Fármacos , Humanos , Indolizinas/química , Concentração Inibidora 50 , Nitrogênio/química , Ftalazinas/química , Inibidores da Topoisomerase I/químicaRESUMO
A series of graveoline and graveolinine derivatives were synthesized. The biological results showed that most of graveoline derivatives possessed higher cytotoxicity and better inhibitive effect against the adhesion and migration of human umbilical vein endothelial cell (HUVEC) than graveolinine derivatives. Among these compounds, 8d was the most potent agents that also showed significant anti-angiogenesis activities in chick embryo chorioallantoic membrane (CAM) assay.
