RESUMO
Camptothecin consists of a lactone E-ring adjacent to a tetracyclic A-D ring planar chromophore which are essential for topoisomerase I inhibition and DNA interaction, respectively. The A-D ring system can be exploited to develop DNA-binding molecules. Indolizino[1,2-b]quinoline derivatives substituted with a piperidinoethyloxy side chain on the A-ring and an aminomethyl function on the D one were synthesized and their DNA-binding properties and in vitro cytotoxicity investigated.
Assuntos
Antineoplásicos/síntese química , Camptotecina/análogos & derivados , Camptotecina/síntese química , DNA/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Camptotecina/química , Camptotecina/farmacologia , Bovinos , Sobrevivência Celular/efeitos dos fármacos , DNA/metabolismo , Pegada de DNA , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , Masculino , Neoplasias da Próstata/patologia , Relação Estrutura-Atividade , Timo/metabolismo , Células Tumorais CultivadasRESUMO
Camptothecin consists of a lactone E ring adjacent to tetracyclic A-D rings of a planar chromophore, which are essential for topoisomerase I inhibition and DNA interaction. The A-D rings can be exploited to develop DNA-sequence-reading molecules. Indolizino[1,2-b]quinoline derivatives substituted with a piperidinoethyloxy side chain and an aminomethyl function on rings A and D, respectively, were synthesized, and their DNA binding and formaldehyde-mediated bonding properties were investigated.