Two novel antifungals SCH 643432 (1), and 2, were isolated from the fermentation broth of a fungus taxonomically classified as a Paecilomyces varioti. These compounds were separated from the fermentation broth filtrate by adsorption on a macroreticular resin XAD-16 (Amberlite). Purification and separation of the individual compounds were achieved by trituration of the extract with dichloromethane followed by preparative HPLC using reverse phase columns. Extensive FAB (Fast Atom Bombardment) and ESI (Electro Spray) mass spectrometric studies using fragmentation of various daughter ions, NMR experiments and degradative studies helped in elucidating the structure of compound 1. Compound 2 is an isomer of SCH 643432 (1). They were identified as straight chains peptides containing several amino acids such as alanine, aminoisobutyric acid, proline, leucine, glycine and arginine. The N-terminal is terminated in a previously identified β-keto acid, 2-methyl 3-oxo tetradecanoic acid (MOTDA).5) Both compounds were active against Candida albicans, other Candidas, dermatophytes and Aspergillus (Geometric Mean MIC's 4.00, 2.59, 3.56, 11.31 and 4.49, 4.00, 5.66, 16.0μg/ml, respectively for 1 and 2).
Three new pentaene macrolides having a 28-membered ring, designated takanawaenes A, B and C, were isolated from the fermentation broth of Streptomyces sp. K99-5278 by solvent extraction, silica-gel column chromatography and HPLC. Takanawaenes showed antifungal activity against Aspergillus niger, Mucor racemosus, Candida albicans and Saccharomyces cerevisiae.
The structures of takanawaenes A, B and C, novel antifungal antibiotics produced by Streptomyces sp. K99-5278, were elucidated by various spectroscopic analyses including UV and NMR, and spectrometric analyses including MS. They have the common skeleton of a 28-membered pentaene macrolide.
In the screening of fungi for bioactive components, 8-O-methylaverufin (1b) and 1, 8-O-dimethylaverantin (2b) were isolated from the culture broth of Penicillium chrysogenum. The structure of these new antibiotics were determined by interpretation of the 1D and 2D NMR spectra and by comparison of the NMR data with those of the structurally related averufin (1a) and averantin (2a). Both compounds have moderate antifungal activity.
EI-1941-1 and -2 isolated from the culture broths of Farrowia sp. selectively inhibited the human recombinant ICE activity with IC50 values of 0.086 and 0.006μM, respectively, without inhibiting elastase and cathepsin B. EI-1941-1 and -2 also inhibited mature interleukin-1β secretion from THP-1 cells induced by LPS with IC50 values of 5.0 and 10.3μM, respectively. Biochemical characterizations of EI-1941-1 and-2 are described in this article.
A number of 13-alkoxy milbemycin derivatives were synthesized to evaluate their anthelmintic activity. We report the strategy for developing a potent anthelmintic product, 13-[4-(N-methanesulfonyl-N-methylamino)-phenylethyloxy]milbemycin. The details of the structure-activity relationships of those derivatives are also discussed.
Synthesis is described for the haptens 23-demycinosyl-23-deoxy-23-(3-aminoprop-l-yl)-aminotilmicosin (6) from 5-O-mycaminosyltylonolide (OMT) and for 23-demycinosyl-23-deoxy-23-(3-aminoprop-1-yl)-amino-20-dihydrotylosin (10) from demycinosyltylosin (DMT), respectively. The mild reaction conditions used to synthesize the second hapten, DMT derivative 10, were necessary to overcome instabilities and acid lability of DMT. The haptens synthesized here may be further used to produce protein conjugates useful in developing antibodies against the antibiotics tilmicosin and tylosin.