RESUMO
Novel analogs of indolylmaleimide derivatives (IM derivatives) were synthesized and tested for cell death-inhibitory activity. 2-(1H-Indol-3-yl)-3-pentylamino-maleimide IM-54 was the most effective cell death inhibitor among the compounds tested. IM-54 inhibited necrotic cell death induced by H2O2, but not apoptotic cell death induced by etoposide. These results indicated that this novel cell death inhibitor is distinct from the well-known caspase inhibitor, Z-VAD, which can block apoptotic cell death, but not necrotic cell death. IM-54 is expected to be a powerful bioprobe for clarifying the unique signaling pathway of necrotic cell death.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Indóis/química , Indóis/farmacologia , Maleimidas/química , Maleimidas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Etoposídeo/farmacologia , Células HL-60/efeitos dos fármacos , Células HL-60/patologia , Humanos , Peróxido de Hidrogênio/farmacologia , Indóis/síntese química , Maleimidas/síntese química , Estrutura Molecular , Necrose , Oxidantes/farmacologia , Proteínas Quinases/química , Relação Estrutura-AtividadeRESUMO
A series of N-methyl-bisindolylmaleimide derivatives was synthesized and evaluated as cell death inhibitors. N-Methyl-2-[1-(3-aminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)maleimide (21) was the most potent inhibitor of H2O2-induced necrotic death of human leukemia HL60 cells among them.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Indóis/química , Indóis/farmacologia , Maleimidas/química , Maleimidas/farmacologia , Antineoplásicos/síntese química , Inibidores Enzimáticos/farmacologia , Células HL-60/efeitos dos fármacos , Células HL-60/patologia , Humanos , Peróxido de Hidrogênio/farmacologia , Indóis/síntese química , Maleimidas/síntese química , Estrutura Molecular , Necrose , Oxidantes/farmacologia , Proteínas Quinases/química , Relação Estrutura-AtividadeRESUMO
[formula: see text] A convenient method for the synthesis of carbamates using polymer-supported N-hydroxysuccinimide is described. Various carbamates were synthesized in highly pure form without the need for chromatographic purification. This new "catch and release"-type solid-phase synthesis should be useful for combinatorial synthesis of various carbamates.
