RESUMO
6-(5-Cholesten-3 beta-yloxy)hexyl 1-thio-beta-D-mannopyranoside (L-644,257) enhances natural host resistance in cyclophosphamide-treated mice against Pseudomonas aeruginosa in a dose-dependent manner. It is active sc, im, and ip but not orally. L-644,257 is substantially more protective against P. aeruginosa than its alpha anomer. The beta-L-fucose glycolipid is more effective when given im and ip than sc. The lactose and beta-D-glucose glycolipids were only marginally effective to nonprotective. The 17 beta-steroidal side chain of L-644,257 can be modified without substantial loss of protective activity.
Assuntos
Adjuvantes Imunológicos , Colesterol/análogos & derivados , Glicolipídeos/farmacologia , Infecções Oportunistas/terapia , Animais , Fenômenos Químicos , Química , Colesterol/síntese química , Colesterol/farmacologia , Relação Dose-Resposta a Droga , Feminino , Glicolipídeos/efeitos adversos , Imunoterapia , Camundongos , Infecções por Pseudomonas/terapia , Relação Estrutura-AtividadeRESUMO
A new class of tricyclic arylacetic acids was synthesized and evaluated as antiinflammatory/analgesic agents as well as inhibitors of prostaglandin synthetase. 11H-Dibenzo[b,e][1,4]dioxepin-2-, -3, -7, and -8-acetic and alpha-methylacetic acids and their derivatives were prepared by cyclization of diaryl ether precursors or by condensation of catechol and an aryl dihalide. The most potent compound in the carrageenan foot edema assay was alpha-methyl-11H-dibenzo[b,e][1,4]dioxepin-8-acetic acid (1 mg/kg = 43% inhibition). The most potent enzyme inhibitors were the 2-acetic acid and the alpha-methyl-7-acetic acid (IC50 = 0.1 microM). Some of these compounds were also found to be highly ulcerogenic.