Sch 54445: a new polycyclic xanthone with highly potent antifungal activity produced by Actinoplanes sp.

A novel antifungal agent, Sch 54445, was isolated from the fermentation broth of an Actinoplanes species. Sch 54445 was identified as a polycyclic xanthone related to the albofungin family of compounds on the basis of analyses of spectroscopic data. As a broad-spectrum antifungal agent, Sch 54445 exhibits highly potent activities against various yeasts and dermatophytes with MIC values approximately 0.00038 microgram/mL.

Inhibition of c-fos proto-oncogene induction by Sch 52900 and Sch 52901, novel diketopiperazine produced by Gliocladium sp.

Sch 52900 (1) and Sch 52901 (2), two new inhibitors of c-fos proto-oncogene induction, have been isolated from the fermentation of broth of the fungal culture (SCF-1168), Gliocladium sp. Along with compounds 1 and 2, a known compound verticillin A (3) was also obtained from the culture. Structure elucidation of 1 and 2, accomplished by analysis of spectral data in comparison with the data of 3, revealed both 1 and 2 were found to be closely related to the verticillin family of diketopiperazines. All three compounds prevented serum-stimulated transcription of the human c-fos promoter, using a fos/lac Z reporter gene assay, with IC50 values of 1.5, 18 and 0.5 microM of 1, 2 and 3, respectively. Northern analysis revealed the exposure of cells to compound 3 causes inhibition of both phorbol ester-induced c-fos induction of serum-induced JE induction in the absence of inhibiting RNA synthesis, as measured by [3H]uridine incorporation. There results suggest that this class of compounds exerts antitumor activity by blocking a signal transduction pathway that is common to and necessary for the induction of at least a subset of immediate early genes involved in cell proliferation.

A novel class of platelet activating factor antagonists from Phoma sp.

Four novel platelet activating factor (PAF) antagonists, Sch 47918, Sch 49026, Sch 49027 and Sch 49028, were isolated from the fermentation broth of the fungal culture, Phoma sp. (ATCC 74077). The structures of these compounds were elucidated by spectroscopic methods. The structure and stereochemistry of the first isolated component, Sch 47918, were confirmed by single crystal X-ray diffraction analysis. Sch 49028, the most active component, was found to inhibit PAF-induced human platelet aggregation in vitro with an IC50 of 1.26 microM. However, this compound was inactive in vivo at 5 mg/kg, iv against PAF-induced bronchospasm in guinea pigs.

Macrolactams: two novel homologous series of compounds produced by Actinomadura sp. SCC 1778.

Eight antifungal compounds were identified from the fermentation of Actinomadura sp. SCC 1778. This culture produces four homologous compounds (C22H42N2O5 approximately C25H48N2O5) containing the sugar, mycosamine, and four homologous compounds (C22H42N2O5 approximately C25H48N2O5) containing the sugar, 3,6-dideoxy-3-amino-L-talopyranose. Five of the compounds identified were novel macrolactams. All these compounds exhibit antifungal activity against Candida spp. with geometric mean MICs ranging from approximately 1.0 micrograms/ml for the higher homologs to 30 micrograms/ml for the lower homologs.

Sch 42137, a novel antifungal antibiotic from an Actinoplanes sp. Fermentation, isolation, structure and biological properties.

A novel polycyclic xanthone, Sch 42137, related to the albofungin family of compounds was isolated from culture broth. Its structure was determined by detailed spectroscopic studies and comparison of circular dichroic studies to related compounds albofungin and simaomicin. Sch 42137 exhibited MIC values less than 0.125 micrograms/ml against yeasts and dermatophytes. Details are presented herein.

Characterization of peptidyl-nucleoside antifungal antibiotics from fermentation broth.

Characterization of sinefungin related antifungal antibiotics from fermentation broth was accomplished by coupling photodiode array (PDA) detection to high performance liquid chromatography (HPLC). From the combined HPLC-PDA evaluation of broth filtrate, we detected five sinefungin related components. Fast atom bombardment (FAB) mass spectroscopic evaluations, mass-analysed ion kinetic energy spectra (MIKES) and collision activated (CA) MIKES of these components confirmed their respective identities. Our findings from the combination of HPLC photodiode array acquisition and FAB-mass spectrometry suggest we have detected the presence of a previously unreported sinefungin analogue.

Sch 37137, a novel antifungal compound produced by a Micromonospora sp. Taxonomy, fermentation, isolation, structure and biological properties.

A new antifungal compound, Sch 37137, was isolated from the cultured broth of a Micromonospora sp., SCC 1792. Sch 37137 is structurally related to A 19009, a dipeptide previously discovered from a Streptomyces sp. The compound was weakly active against species of Candida and dermatophytes (mean MICs greater than or equal to 128 micrograms/ml) in Sabouraud dextrose, yeast-nitrogen and modified Eagles minimum essential media; however activity against Candida sp. (mean MICs greater than or equal to 12 micrograms/ml) and dermatophytes (mean MICs greater than or equal to 0.8 microgram/ml) significantly improved in MA medium.