RESUMO
Benzo[c]phenanthrolines and benzo[c]phenanthrolinones substituted by dialkylaminoalkyl side chains at position N5 and C6, respectively, were synthesised and their biological activity evaluated. They displayed interessant cytotoxicity associated with some DNA interactions. However, the low topoisomerase 1 affinity suggests that other cellular targets are responsible for the antiproliferative activity.
Assuntos
Antineoplásicos/farmacologia , Fenantrolinas/farmacologia , Inibidores da Topoisomerase I/farmacologia , Inibidores da Topoisomerase II/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Bovinos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , DNA/química , DNA/efeitos dos fármacos , DNA Topoisomerases Tipo I/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HT29 , Humanos , Estrutura Molecular , Fenantrolinas/síntese química , Fenantrolinas/química , Estereoisomerismo , Relação Estrutura-Atividade , Inibidores da Topoisomerase I/síntese química , Inibidores da Topoisomerase I/química , Inibidores da Topoisomerase II/síntese química , Inibidores da Topoisomerase II/químicaRESUMO
Benzo[c][1,7] and [1,8]phenanthroline substituted by dialkylaminoalkyl side chains at position C2 and C1, respectively, were synthesized and their biological activity evaluated. These compounds displayed more potent cytotoxicity toward L1210 cells than the parent unsubstituted compounds, associated with strong DNA interaction. The moderate TopoI inhibitory activity induced by the novel compounds suggests that other cellular targets should be responsible for the antiproliferative activity.