RESUMO
Three series of indeno[1,2-c]isoquinolines bearing a ferrocenyl entity were synthesized and evaluated for DNA interaction, topoisomerase I and II inhibition, and cytotoxicity against breast human cancer cell lines. In the first and second series, the ferrocenyl scaffold was inserted as a linker between the two nitrogen atoms. In the last series, it was introduced at the end of the carbon chain. The present study showed that the ferrocenyl entity enhanced the topoisomerase II inhibition. Most compounds showed a potent growth inhibitory effect on MDA-MB-231 cell line with the IC50 in µM range.
Assuntos
Antineoplásicos/farmacologia , Proteínas de Ligação a DNA/antagonistas & inibidores , Compostos Ferrosos/síntese química , Compostos Ferrosos/farmacologia , Isoquinolinas/síntese química , Isoquinolinas/farmacologia , Inibidores da Topoisomerase II/síntese química , Inibidores da Topoisomerase II/farmacologia , Antígenos de Neoplasias/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Ferrosos/química , Humanos , Concentração Inibidora 50 , Isoquinolinas/química , Estrutura Molecular , Relação Estrutura-Atividade , Inibidores da Topoisomerase II/química , Células Tumorais CultivadasRESUMO
The first enantioselective synthesis of 4-aza-podophyllotoxin derivatives by partial transfer hydrogenation of lactone-fused quinolines was achieved using a chiral Brønsted acid catalyst. This reaction was extended to a large scope of substrates with good yields and enantioselectivities.
