Two novel antitumor alkaloids, Stephacidin A and B, were isolated from the solid fermentation of Aspergillus ochraceus WC76466. Both alkaloids exhibit in vitro cytotoxicity against a number of human tumor cell lines; however, stephacidin B demonstrated more potent and selective antitumor activities, especially against prostate testeosterone-dependent LNCaP cells with IC50 value of 60 nM. The structures of stephacidin A and B were established on the basis of the NMR data and X-ray crystallography. With 15 rings and 9 chiral centers, stephacidin B represents one of the most structurally complex and novel alkaloids occurring in nature.

Bacillaene, a novel polyene antibiotic, was discovered and isolated from fermentation broths of a strain of Bacillus subtilis. The novel antibiotic has a nominal molecular weight of 580 and an empirical formula of C3 5H48O7.Bacillaene is active against a broad spectrum of bacteria in agar-plate diffusion assays. Studies in vitro indicate that the antibiotic inhibits prokaryotic protein synthesis but not eukaryotic protein synthesis. Cell survival studies performed with strains of Escherichia coli indicate that the antibiotic is a bacteriostatic agent.

Indole derivative 1 interferes with the interaction of the HIV surface protein gp120 with the host cell receptor CD4. The 4-fluoro derivative 2 exhibited markedly enhanced potency and was bioavailable in the rat, dog, and cynomolgus monkey when administered orally as a solution formulation. However, aqueous suspensions of 2 were poorly bioavailable, indicative of dissolution-limited absorption. The 7-azaindole derivative 3, BMS-378806, exhibited improved pharmaceutical properties while retaining the HIV-1 inhibitory profile of 2.

The new cytotoxic agents rakicidins A and B were isolated from cultured broth of a Micromonospora sp. Spectroscopic and amino acid analysis has shown that rakicidin A is a new cyclic lipopeptide, consisting of 4-amino-penta-2,4-dienoic acid, 3-hydroxy-2,4,16-trimethylheptadecanoic acid, sarcosine, and 3-hydroxyasparagine. Rakicidin B differs by one methylene group in the lipid side chain. These compounds exhibited cytotoxicity against the Ml09 cell line. In our continuing search for newantitumor agents from microorganisms, an isolate of Micromonospora was selected for further evaluation. This research led to the discovery of two newcytotoxic lipopeptides, rakicidins A and B (Fig. 1). This paper describes the fermentation, biological evaluation, purification, physico-chemical characterization, and structure elucidation of these compounds. Fermentation Microorganism The producing organism was isolated from a soil sample collected at Andhra Pradesh, India and was identified as a Micromonospora sp., strain No. R385-2. Media and Culture Conditions Micromonospora strain No. R385-2 was grown on slants of modified Bennett's mediumwhich contained the following: 0.5% Japanese potato starch (Generichem DEC. 1995 Corp. Acadama Dextrin No. 3), 0.5% glucose, 0.1% fish meat extract (Mikuni Chem. Industry), 0.1% yeast extract (Difco), 0.2% N-Z Case (Sheffield Products), 0.2% NaCl, 0.1% CaCO3, 1.5% agar. The medium was sterilized at 121°C for 20 minutes. The culture was transferred from the slant into 100ml of GERmedium in a 500ml flask. The medium contained the following: 2.4% Japanese potato starch, 0.1% dextrose, 0.3% beef extract (BBL), 0.5% tryptone (Difco), 0.5% yeast extract (BBL), 0.2% CaCO3 and was adjusted to pH 7.6 before autoclaving. The mediumwas sterilized at 121°C for 20

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