RESUMO
Brand new ring: A series of 27 derivatives of the new ring system [1,2]oxazolo[4,5-g]indole were conveniently prepared and tested at the NCI for antiproliferative studies. Several of them showed good inhibitory activity toward all tested cell lines, reaching GI50 values generally at the micromolar and sub-micromolar levels and in some cases at nanomolar concentrations. The mean GI50 values, calculated on the full panel, were in the range 0.25-7.08â µM.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Indóis/química , Indóis/farmacologia , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indóis/síntese química , Neoplasias/tratamento farmacológico , Oxazóis/síntese química , Oxazóis/química , Oxazóis/farmacologia , Relação Estrutura-AtividadeRESUMO
Heteroanalogues of angelicin, pyrrolo[3,2-h]quinazolines, were synthesized with the aim of obtaining new potent photochemotherapeutic agents. Many derivatives caused a significant decrease in cell proliferation in several human tumor cell lines after irradiation with UVA light (GI(50) =15.2-0.2 µM). Their phototoxicity effected apoptosis in Jurkat cells with the involvement of mitochondria (as determined by the loss of mitochondrial membrane potential and production of reactive oxygen species) and lysosomes. The phototoxicity of these compounds could be explained by lipid peroxidation.
Assuntos
Fármacos Fotossensibilizantes/química , Pirróis/química , Quinolinas/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Furocumarinas/síntese química , Furocumarinas/química , Furocumarinas/toxicidade , Humanos , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/toxicidade , Pirróis/síntese química , Pirróis/toxicidade , Quinolinas/síntese química , Quinolinas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Raios UltravioletaRESUMO
In the search for new photochemotherapeutic agents, a series of derivatives of the ring system pyrrolo[3,2-h]quinoline--bioisosters of the angular furocoumarin angelicin--were synthesized through a four-step synthetic approach, in reasonable overall yields. Eight of the synthesized derivatives showed a remarkable phototoxicity against a panel of four human tumor cell lines and a great dose UV-A dependence, reaching IC50 values at submicromolar level. The mode of cellular death photoinduced by pyrrolo[3,2-h]quinolines was evaluated through a series of flow cytometric analysis and other tests were performed to clarify their mechanism of action.
