RESUMEN
A series of condensed N-aryl-2-cyano-3-oxo-3-pyrazolyl-propanamides were synthesized and evaluated for immunomodulating activity following intraperitoneal administration. These new molecules were found to enhance macrophage cytotoxicity and stimulate host mediated antibacterial defences in mice. The compound 3-cyano-3-(1,4-dihydro-1-phenyl-[1]-benzothiopyrano[4,3-c]pyrazol- 3-yl]-3-oxo-N-phenyl-propanamide, chosen for wider pharmacological investigation, proved effective in preventing adjuvant-induced arthritis development in rats.
Asunto(s)
Adyuvantes Inmunológicos/síntesis química , Nitrilos/síntesis química , Pirazoles/síntesis química , Adyuvantes Inmunológicos/farmacología , Animales , Artritis Experimental/prevención & control , Pruebas Inmunológicas de Citotoxicidad , Femenino , Macrófagos/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Nitrilos/farmacología , Infecciones por Pseudomonas/inmunología , Infecciones por Pseudomonas/prevención & control , Pirazoles/farmacologíaRESUMEN
The effect of cyclosporin A (CSA) on the antibody response to pneumococcal polysaccharide type III (a T-independent class 2 antigen) was investigated in mice. A single oral CSA administration (50 mg/kg) was able to depress (40%) the primary antibody response evaluated as spleen plaque-forming cells. Repeated treatments (12-50 mg/kg x 5) resulted in a higher degree of inhibition (80%) of anti-SIII response. Both single and repeated CSA treatments were active only when administered concomitantly with or after immunization, whereas no effects were seen with drug pretreatment. Comparable inhibitions of anti-SIII response were observed in control and nude mice suggesting a direct effect of CSA on B-cells.