The ethyl acetate extract from the Streptomyces sp. isolate B8652 delivered the trioxacarcins A-C (2a-2c) and additionally three new derivatives designated as trioxacarcins D-F (2d-2f). All trioxacarcins showed high anti-bacterial and some of them high anti-tumor and anti-malaria activity. The structures of the new antibiotics were derived from mass, 1D and 2D NMR spectra and confirmed by comparison of the NMR data with those of known derivatives. The absolute configuration of the trioxacarcins is deduced from the X-ray analysis of gutingimycin (2g) and from the known stereochemistry of the L-trioxacarcinoses A and B.
A novel antifungal antibiotic, FR227244, was isolated from the culture broth of a fungal strain No. 002. The strain was identified as Myrothecium cinctum from morphological and physiological characteristics. This compound was isolated from the culture broth by solvent extraction, HP-20 and YMC ODS gel column chromatographies, and n-hexane precipitation. FR227244 is a white powder which melts at 210-211°C and possesses the molecular formula C38H58O11. FR227244 is a novel triterpene glycoside with antifungal activity against Aspergillus fumigatus. The effects of FR227244 on the morphology of A. fumigatus were shown to be similar to those of FR901379 which is a known 1, 3-β-glucan synthase inhibitor.
FR227244 is a novel triterpene glycoside that exhibits in vitro antifungal activity against filamentous fungi such as Aspergillus sp. and Trichophyton sp. and yeast such as Candida utilis and Candida parapsilosis but shows low activity against Candida albicans, Candida krusei and Candida tropicalis. Specifically, FR227244 exhibits in vitro and in vivo antifungal activity against Aspergillus fumigatus. The minimum effective concentration (MEC) of FR227244 against A. fumigatus FP1305 in a micro-broth dilution test was 0.031μg/ml. FR227244 showed good efficacy by subcutaneous injection and oral administration against A. fumigatus in a murine systemic infection model, with ED50s of 1.9 and 18mg/kg, respectively. FR227244 inhibited glucan synthesis in a 1, 3-β-glucan synthase assay weakly and in whole cells strongly, but did not effect other macromolecule synthesis, including protein, nucleic acids, mannan and chitin. These results and the effect on hyphal morphology of A. fumigatus suggested that FR227244 showed antifungal activity based on inhibition of glucan synthesis.
A new thiazolidine-type antibiotic with zinc in its structure, designated transvalencin A, was isolated from Nocardia sp. IFM 10065, a clinical isolate from a patient with actinomycotic mycetoma. The strain was identified as Nocardia transvalensis based on its morphological, phenotypic and phylogenetic characteristics. Transvalencin A showed antimicrobial activity against fungi such as Trichophyton mentagrophytes and Cryptococcus neoformans. The antibiotic is also active against Gram-positive bacteria such as Micrococcus luteus. We observed higher activity for fungi in an acidic medium than in a neutral medium.