ABSTRACT
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.
Subject(s)
Bridged Bicyclo Compounds/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Hydroxamic Acids/chemical synthesis , Matrix Metalloproteinase Inhibitors , Receptors, IgE/metabolism , Bridged Bicyclo Compounds/pharmacology , Enzyme Inhibitors/pharmacology , Hydroxamic Acids/pharmacology , Molecular Structure , Receptors, IgE/antagonists & inhibitors , Structure-Activity RelationshipABSTRACT
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.
Subject(s)
Anacardic Acids , Plants/chemistry , Salicylates/isolation & purification , beta-Lactamase Inhibitors , Chromatography, High Pressure Liquid , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/enzymology , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Molecular Conformation , Plant Extracts/pharmacology , Salicylates/pharmacologyABSTRACT
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.
Subject(s)
Actinomycetales/chemistry , Anti-Bacterial Agents , Anti-Bacterial Agents/isolation & purification , Glycopeptides/isolation & purification , Anti-Bacterial Agents/pharmacology , Glycopeptides/chemistry , Glycopeptides/pharmacology , Gram-Positive Bacteria/drug effects , Microbial Sensitivity Tests , Ristocetin/analogs & derivatives , Structure-Activity RelationshipABSTRACT
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.
