Salfredins, new aldose reductase inhibitors produced by Crucibulum sp. RF-3817. I. Fermentation, isolation and structures of salfredins.

New inhibitors of aldose reductase, designated salfredins A3, A4, A7, C1, C2, C3 and B11, were isolated from the fermentation broth of Crucibulum sp. RF-3817 by successive purification procedures of solvent extraction, silica gel column chromatographies and reverse-phase HPLC. Their structures were established by spectroscopic methods, including UV, SI-MS and NMR. The structures of salfredins A4 and B11 were confirmed by X-ray crystallographic analysis.

Isolation and biological activity of thielocins: novel phospholipase A2 inhibitors produced by Thielavia terricola RF-143.

Thielocins A2 alpha, A2 beta, A3, B1, B2 and B3 were isolated as a novel family of phospholipase A2 inhibitors from the fermentation broth of Thielavia terricola RF-143 together with thielavins and thielocins A1 alpha and A1 beta. The most potent inhibitory activity (IC50 = 0.0033 microM) against rat group II phospholipase A2 was shown by thielocin A1 beta. Against human group II phospholipase A2, thielocin B3 (IC50 = 0.076 microM) was the most potent.

Depudecin: a novel compound inducing the flat phenotype of NIH3T3 cells doubly transformed by ras- and src-oncogene, produced by Alternaria brassicicola.

A novel compound depudecin inducing the flat phenotype of ras- and src- transformed NIH3T3 cells at a concentration of 1 microgram/ml was isolated from the culture broth of Alternaria brassicicola. Based on its spectroscopic characteristics and X-ray crystallographic analysis of its bis-(1S)-(-)-camphanate, the structure of depudecin was determined to be (2R,3S,4S,5E,7S,8S,9R)-2,9- dihydroxy-3,4;7,8-diepoxy-undeca-5,10-diene.

Isolation and structural elucidation of new cyclotetrapeptides, trapoxins A and B, having detransformation activities as antitumor agents.

New cyclotetrapeptides, trapoxins A and B were isolated from the culture broth of Helicoma ambiens RF-1023. These compounds exhibit detransformation activities against v-sis oncogene-transformed NIH3T3 cells (sis/NIH3T3) as antitumor agents. The structures were found to be new cyclotetrapeptides, cyclo[(S)-phenylalanyl-(S)-phenylalanyl-(R)-pipecolinyl- (2S,9S)-2-amino-8-oxo-9,10-epoxydecanoyl-] for trapoxin A and cyclo[(S)-phenylalanyl-(S)-phenylalanyl-(R)-prolyl-2- amino-8-oxo-9,10-epoxydecanoyl-] for trapoxin B, by X-ray analysis, mass spectrometric, NMR and chemical studies.

Isolation and characterization of agglomerins A, B, C and D.

New antibiotics, agglomerins A, B, C and D, were isolated from the culture broth of a bacterial strain identified as Enterobacter agglomerans. These antibiotics are acidic in nature and their sodium salts are obtained as colorless crystalline powders, soluble in lower alcohols. All the antibiotics shows characteristic UV maxima at 248 and 298 nm. Molecular formulas: A, C15H21O4Na; B, C17H23O4Na; C, C17H25O4Na and D, C19H27O4Na; were indicated by elemental analysis and MS. These antibiotics are active against a wide variety of anaerobic bacteria and weakly against aerobic Gram-positive bacteria in vitro.

Enzymatic reduction of synthetic polymer-bound hemin derivatives: efficient method to prepare a heme-oxygen adduct in cooled aqueous medium.

Synthetic polymer-bound hemin (iron(III) protoporphyrin IX) derivatives were effectively reduced by ferredoxin and ferredoxin-NADP reductase system. The resultant polymer-bound heme (iron(II) protoporphyrin IX) derivatives formed oxygen adducts with a lifetime of ca. 1 hr in aqueous solution at -30 degrees C. The reduction rate is discussed in terms of the structure of the hemin derivatives.