RESUMEN
Using a variety of alpha-hydroxy hydroxamic acid derivatives, the size and shape of the S1' pocket for the CD23 processing metalloprotease has been explored. It has been demonstrated that a P1' 2-naphthylmethyl group occupies most of the available space and gives excellent selectivity against fibroblast collagenase (matrix metalloproteinase-1, MMP-1) and other MMPs.
Asunto(s)
Compuestos Bicíclicos con Puentes/síntesis química , Inhibidores Enzimáticos/síntesis química , Ácidos Hidroxámicos/síntesis química , Inhibidores de la Metaloproteinasa de la Matriz , Receptores de IgE/metabolismo , Compuestos Bicíclicos con Puentes/farmacología , Inhibidores Enzimáticos/farmacología , Ácidos Hidroxámicos/farmacología , Estructura Molecular , Receptores de IgE/antagonistas & inhibidores , Relación Estructura-ActividadRESUMEN
SB-202742 [1], an anacardic acid derivative possessing beta-lactamase inhibitory activity, has been isolated from a hexane extract of the plant, Spondias mombin. Its isolation, structure determination, and biological activity are reported herein.
Asunto(s)
Ácidos Anacárdicos , Plantas/química , Salicilatos/aislamiento & purificación , Inhibidores de beta-Lactamasas , Cromatografía Líquida de Alta Presión , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/enzimología , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Conformación Molecular , Extractos Vegetales/farmacología , Salicilatos/farmacologíaRESUMEN
Two novel glycopeptide antibiotics MM 55266 and MM 55268 containing fatty acid acyl functions, and of molecular formula C86H89N8O35Cl5 and C87H91N8O35Cl5, respectively, have been isolated and identified from a complex produced by Amycolatopsis sp. NCIB 40089. Fermentation conditions for their production, and methods for their isolation are described. Structures have been deduced by use of COSY and NOE NMR techniques and supported by chemical degradation studies. Both glycopeptides possessed good antibacterial activity against Gram-positive organisms.
Asunto(s)
Actinomycetales/química , Antibacterianos , Antibacterianos/aislamiento & purificación , Glicopéptidos/aislamiento & purificación , Antibacterianos/farmacología , Glicopéptidos/química , Glicopéptidos/farmacología , Bacterias Grampositivas/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Ristocetina/análogos & derivados , Relación Estructura-ActividadRESUMEN
The synthesis and antibacterial activity of 7 beta-[D-2-(aryl)-2-[(4-ethyl-2,3-dioxopiperazin-1-yl) carbonylamino] acetamido]-7 alpha-formamidocephalosporins with various substituents at the C-3 position of the cephalosporin nucleus is described. Inhibition of Gram-positive and Gram-negative bacteria including beta-lactamase producing strains was observed with phenyl as the aryl residue. The 3,4-dihydroxyphenyl group further enhanced the activity against Gram-negative organisms; in this series, the 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl] and 3-[(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl] analogues (2 and 12b) exhibited exceptional activity against Gram-negative bacteria, including Pseudomonas aeruginosa.