Chemistry of enzyme inhibitors of microbial origin

Abstract

Study of antibiotics has furnished interesting materials to chemistry of natural products. I initiated the screening study of enzyme inhibitors produced by microorganisms and isolated leupeptin and antipain inhibiting trypsin and papain, chymostatin inhibiting chymotrypsin, pepstatin inhibiting pepsin, panosialin inhibiting sialidases, oudenone inhibiting tyrosine hydroxylase, dopastin inhibiting dopamine β-hydroxylase, aquayamycin and chrothiomycin inhibiting tyrosine hydroxylase and dopamine β-hydroxylase. Structures and syntheses of most of these compounds have been studied. I also found dopamine β-hydroxylase-inhibiting activity of fusaric acid and oosponol, and xanthineoxidase inhibiting activity of 5-formyluracil which were produced by microorganisms. Chemical study of enzyme inhibitors has given useful information on the structure/activity relation. The effect of pepstatin on stomach ulcer, and the hypotensive effect of oudenone and fusaric acid have been observed clinically. Enzyme inhibitors produced by microorganisms are the most valuable new area extended from antibiotics and will furnish new materials interesting in chemistry. biosynthesis, pharmacology, and utility. © 1973, Walter de Gruyter. All rights reserved.