A potent nonpeptide cholecystokinin antagonist selective for peripheral tissues isolated from Aspergillus alliaceus.

A new, competitive, nonpeptide cholecystokinin (CCK) antagonist, asperlicin, was isolated from the fungus Aspergillus alliaceus. The compound has 300 to 400 times the affinity for pancreatic, ileal, and gallbladder CCK receptors than proglumide, a standard agent of this class. Moreover, asperlicin is highly selective for peripheral CCK receptors relative to brain CCK and gastrin receptors. Since asperlicin also exhibits long-lasting CCK antagonist activity in vivo, it should provide a valuable tool for investigating the physiological and pharmacological actions of CCK.

Microbial hydroxylation and glucuronidation of the angiotensin II (AII) receptor antagonist MK 954.

The microbial metabolism of MK 954 (Fig. 1), a novel nonpeptide angiotensin II receptor antagonist, was investigated using 40 microorganisms in an initial screen for cultures that will produce metabolites similar to those produced in the mammalian liver. The microbial transformation occurred under aerobic conditions in shake flasks incubated at 27 degrees C. Three metabolites of MK 954 were isolated and identified as the 1'-hydroxy M2, 3'-hydroxy M1, and glucuronic acid conjugated M3 derivatives. The structures of the metabolites were established by UV, 1H-NMR spectroscopy and FAB-MS spectrometry and are identical to metabolites produced by incubation of MK 954 with mammalian liver slices.

L-671,329, a new antifungal agent. I. Fermentation and isolation.

In screening for new antifungal agents from fungi, a new lipopeptide antifungal agent, L-671,329, similar to echinocandin B, has been isolated from Zalerion arboricola. Studies indicate that L-671,329 is produced under both solid and liquid fermentation conditions.

Microbial transformation of immunosuppressive compounds. I. Desmethylation of FK506 and immunomycin (FR 900520) by Actinoplanes sp. ATCC 53771.

The immunosuppressants FK506 and FR 900520 were desmethylated by Actinoplanes sp. ATCC 53771 to yield various O-desmethylated products. The products were isolated and purified by solvent extraction and HPLC chromatography, and identified by NMR and MS spectroscopy.

L-681,217, a new and novel member of the efrotomycin family of antibiotics.

L-681,217 is a new broad spectrum antibiotic isolated from fermentation broth. The compound is a structurally unique member of the efrotomycin family of growth permittant antibiotics.

Novel cholecystokinin antagonists from Aspergillus alliaceus. I. Fermentation, isolation, and biological properties.

The discovery and biological properties of four novel cholecystokinin antagonists produced by Aspergillus alliaceus is described. One of these was seven times more potent than the previously reported asperlicin.

[R-(Z)]-4-amino-3-chloro-2-pentenedioic acid, a new antibiotic. Fermentation, isolation and characterization.

A new unsaturated glutamic acid analog, 4-amino-3-chloro-2-pentenedioic acid ( ACPA ) was isolated from a fermentation broth produced by a strain of Streptomyces. ACPA has a very narrow antibacterial spectrum, which is virtually limited to Micrococcus luteus.

L-696,474, a novel cytochalasin as an inhibitor of HIV-1 protease. I. The producing organism and its fermentation.

A novel cytochalasin, L-696,474, (18-dehydroxy cytochalasin H) that inhibits HIV-1 protease was discovered in fermentations of a bark-inhabiting Ascomycete, Hypoxylon fragiforme. The product was first identified from extracts of an agar medium. Fermentation studies on a number of media indicated that the product can be made on several solid and liquid media. Optimum production was obtained from growth in a complex medium composed of glycerol, glucose, citrate, Ardamine, soybean meal, tomato paste, and inorganic salts. Other Hypoxylon spp., related species of Xylariales, and other fungi known to produce cytochalasins, were also surveyed for their ability to make L-696,474. Only one other Hypoxylon fragiforme isolate was found to make this novel cytochalasin; none of the other cultures surveyed made L-696,474 or any other compounds which inhibit HIV-1 protease.

Asperlicin, a novel non-peptidal cholecystokinin antagonist from Aspergillus alliaceus. Fermentation, isolation and biological properties.

The fermentation and isolation of a new, non-peptide cholecystokinin antagonist, asperlicin, produced by Aspergillus alliaceus is described. The potent and specific interaction of asperlicin with cholecystokinin receptors was shown using in vitro biochemical assays.

L-155,175: a new antiparasitic macrolide. Fermentation, isolation and structure.

A new antiparasitic macrolide, L-155,175, produced by a strain of Streptomyces hygroscopicus, has been isolated; its structure was determined by physico-chemical means. It is active against the tapeworm Hymenolepis diminuta in rats.