A new compound, MK800-62F1, was isolated from a cultured broth of Streptomyces diastatochromogenes MK800-62F1. It inhibited H2O2-induced apoptosis in human small cell lung carcinoma Ms-1 cells as well as in human T-cell leukemia Jurkat cells. In addition, MK800-62F1 also inhibited camptothecin-induced apoptosis in Jurkat cells, which was mediated by intracellular H2O2 generation. MK800-62F1 did not exhibit antioxidative activity in vitro, suggesting that inhibition of apoptosis by MK800-62F1 was not due to the scavenging of H2O2, rather it was due to the modulation of the downstream event of H2O2 generation.
A new family of capillary tube formation inhibitors, designated luminacins, has been discovered in the fermentation broth of a soil bacterium. The strain was identified as Streptomyces sp. Mer-VD1207 from taxonomic studies. By means of a series of chromatographic procedures, fourteen structurally related components, luminacins A1, A2, B1, B2, C1, C2, D, E1, E2, E3, F, G1, G2, and H, were isolated, and their structures were elucidated on the basis of spectroscopic analyses.
Twelve of the fourteen isolated components of the luminacin family were assayed for activity to inhibit capillary tube formation in vitro. Seven of them showed potent activity with IC50 values of less than 0.1μg/ml in a rat aorta matrix culture model. Luminacin D, the strongest inhibitor, inhibited both endothelial cell proliferation and capillary tube formation. Morphological observation suggested that luminacin D inhibited the rearrangement of endothelial cells in the initial stage of tube formation. Luminacins and their derivatives are good candidates for application as angiogenesis inhibitors with a novel mechanism of action.
A novel antifungal cyclic depsipeptide termed glomosporin, which has a fatty acyl side chain, was isolated from a barley solid culture of Glomospora sp. The strain was isolated from fallen pine leaves collected in Fukusima Prefecture, Japan and identified as Glomospora sp. BAUA2825. Glomosporin was purified by butanol extraction followed by preparative HPLC. Glomosporin showed antimicrobial activity against fungi including clinically important Aspergillus fumigatus.
A new chitinase inhibitor, named argifin, was isolated from the cultured broth of a fungal strain FTD-0668. The strain was identified as Gliodadium sp. from morphological characteristics. The IC50 value of argifin against Lucilia cuprina chitinase was 3.7μM. Argifin arrested the moult of cockroach larvae upon injection into the ventral abdominal part.
A new chitinase inhibitor, named argifin, was isolated from the cultured broth of a fungal strain Gliodadium sp. FTD-0668. Argifin was purified from the cultured mycelium by the combination of cation exchange, anion exchange, adsorption, and gel filtration chromatographic methods. The structure of argifin was elucidated as cyclo(Nω-(N-methylcarbamoyl)-L-arginyl-N-methyl-L-phcnylalany1-β-l-aspartyl-β-laspartyl-D-alanyl) by NMR experiments and other spectroscopic analyses.
During the course of screening for novel cell cycle inhibitors, FRl 82877 was isolated from the fermentation broth of Streptomyces sp. No.9885. During the NMR measurements, FRl 82877 decomposed so much that the structure elucidation of FRl 82877 itself was difficult. Then, combinations of chemical correlations and spectroscopic methods clarified that FRl 82877 possesses an unprecedented multi-ring system including the strained double bond, which was unexpectedly epoxidized by molecular oxygen. FRl 82877 showed broad antitumor activities in vitro and promoted assemblies of tublins in vitro as well as taxol. It is noteworthy that epoxidation of the distorted double bond resulted in significant decrease in antitumor activities.