RESUMEN
The synthesis of several derivatives of 2H-pyran-3(6H)-ones and their Michael adducts is described. Phenylthio, benzenesulfonyl, p-acetylaminobenzenesulfonyl, and p-bromophenyl substituents are beneficial for activity against gram-positive bacteria. 2-[4-(Phenylthio)phenyl]-2-methyl-6-methoxy-2H-pyran-3(6H)-one (8a) showed a minimum inhibitory concentration of 1.56 micrograms/mL against Staphylococcus aureus ATCC 2593, and 2-[4-(phenylthio)phenyl]-2-methyl-6-[(p-nitrobenzoyl)oxy]-2H-pyran-3 (6H)-one (9) showed a minimum inhibitory concentration of 0.75 microgram/mL against Streptococcus sp. C203M. In general, derivatives of 6-hydroxy-2H-pyran-3(6H)-ones with substituents at C-2 and C-6 showed significant activity against gram-positive bacteria. More specifically, the bulkier the C-2 substituent, the greater the antibacterial activity. Michael adducts of thiols (13) showed activity, which may be due to a retro-Michael reaction. In conclusion, the alpha,beta-enone system is essential for the activity of 6-hydroxy-2H-pyran-3(6H)-ones, and the size and nature of substituents at C-2 are associated with antimicrobial activity.
Asunto(s)
Antibacterianos/síntesis química , Pironas/síntesis química , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Pironas/farmacología , Relación Estructura-ActividadRESUMEN
Daily intraperitoneal doses of concanavalin A (Con A) produced a dose-related inhibition of adjuvant-induced arthritis in rats. Con A was also effective on established arthritis, markedly relieving the disease after only three doses. The inhibitory effect of Con A was neutralised by pre-incubation with ovalbumin, although this treatment did not modify the delayed phlogistic action of Con A in rat paws.
Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Concanavalina A/uso terapéutico , Inmunosupresores/uso terapéutico , Animales , Concanavalina A/efectos adversos , Concanavalina A/metabolismo , Relación Dosis-Respuesta a Droga , Edema/inducido químicamente , Femenino , Pie , Miembro Posterior , Ovalbúmina/metabolismo , Ratas , Factores de TiempoRESUMEN
Synthetic linear dextran of molecular weight 40,000 produces the systemic anaphylactoid reaction in rats although it is about 4 times less active than the natural branched dextran of similar molecular weight. Similarly, it is less active on local injection into the foot or skin. However, in rats which have been bred for non-reactivity to systemic dextran, it is more active on local injection, resembling the activity of a branched natural dextran of much lower molecular weight (6,000). In human skin, the synthetic linear 40,000 sample is also more active than the natural branched sample of similar molecular weight in producing a wheal and erythema. The results suggest that the dextran receptor in the skin of man may be similar to that in rats genetically resistant to systemic dextran.
Asunto(s)
Anafilaxia/etiología , Dextranos , Animales , Permeabilidad Capilar/efectos de los fármacos , Dextranos/administración & dosificación , Dextranos/antagonistas & inhibidores , Femenino , Glucosa/farmacología , Humanos , Inyecciones Intraperitoneales , Inyecciones Intravenosas , Inyecciones Subcutáneas , Leuconostoc , Peso Molecular , RatasRESUMEN
Theobromine sodium salicylate exerts an inhibitory effect on lysis of rabbit red cells by streptolysin O. No similar action of related compounds has been demonstrated.