Novel and potent gastrin and brain cholecystokinin antagonists from Streptomyces olivaceus. Taxonomy, fermentation, isolation, chemical conversions, and physico-chemical and biochemical properties.
1991; Springer Nature; Volume: 44; Issue: 6 Linguagem: Inglês
10.7164/antibiotics.44.613
ISSN1881-1469
AutoresY. K. TONY LAM, Debra L. Bogen, Raymond S.L. Chang, KRISTINE A. FAUST, Otto D. Hensens, Deborah L. Zink, Cheryl D. Schwartz, LORETTA ZITANO, George M Garrity, Magda M. Gagliardi, Sara Currie, H. B. Woodruff,
Tópico(s)Bioactive Compounds and Antitumor Agents
ResumoThe discovery and physico-chemical characterization of three novel and minor virginiamycin M1 analogs as potent gastrin antagonists from a culture of a strain of Streptomyces olivaceus are described. These analogs are L-156,586, L-156,587 and L-156,588. They are, respectively, 15-dihydro-13,14-anhydro-, 13,14-anhydro- and 13-desoxy-analogs of virginiamycin M1. We also chemically converted virginiamycin M1 (via L-156,587) to L-156,586 and its unnatural epimer, L-156,906. These analogs are competitive and selective antagonists of gastrin and brain cholecystokinin binding at nanomolar concentrations. These are the most potent gastrin/brain cholecystokinin antagonists from natural products. The same compounds showed poor Gram-positive antibiotic activity versus virginiamycin M1. Structurally related Gram-positive antibiotics, griseoviridin and madumycin I, were inactive in gastrin and brain cholecystokinin binding at up to 100 microM.
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