RESUMO
The thiazole analogues of the marine bis(indole)alkaloid nortopsentins, 2,4-bis(3-indolyl)thiazoles, were synthesized using Hantzsch reaction between indole-3-thioamides and 3-(alpha-bromoacetyl)indoles as the key step, and these analogues showed potent cytotoxic activities against a variety of human cancer cell lines in vitro.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Tiazóis/síntese química , Tiazóis/farmacologia , Antineoplásicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Relação Estrutura-Atividade , Tiazóis/química , Células Tumorais CultivadasRESUMO
Three HAV variants, H2M20(35 degrees C), H2M20(35 degrees C) and H2M20K5(32 degrees C), were developed by passage in different tissue culture cells and at different temperatures. Virulence for monkeys was assessed by inoculating each of the variants into four monkeys. Weekly bleeding through 16 weeks post-inoculation was assayed for anti-HAV titers and SGPT as well as LDH5 activities. And in some monkeys liver biopsies were also studied. Seroconversion was induced in all of the inoculated monkeys. The anti-HAV titers tested at 16 weeks post-inoculation were: 40-640 with H2M20(35 degrees C), 40-160 with H2M20(32 degrees C) and 20-40 with H2M20K5(32 degrees C). These variants showed different levels of virulence/attenuation for monkeys. Variant H2M20(35 degrees C) showed no evidence of attenuation, variant H2M20(32 degrees C) retained slight virulence and variant H2M20K5(32 degrees C) showed no evidence of virulence for monkeys. Criteria are proposed for assay of HAV virulence tested in monkeys.
