Macbecin

Abstract: Compounds that modulate the heat shock protein (HSP) network have potential in a broad range of research applications and diseases. A yeast-based liquid culture assay that measured time-dependent turbidity enabled the high-throughput screening of different Saccharomyces cerevisae strains to identify HSP modulators with unique molecular mechanisms. A focused set of four strains, with differing sensitivities to Hsp90 inhibitors, was used to screen a compound library of 3680 compounds. Computed turbidity curve functions were used to classify strain responses and sensitivity to chemical effects across the compound library. Filtering based on single-strain selectivity identified nine compounds as potential heat shock modulators, including the known Hsp90 inhibitor macbecin. Haploid yeast deletion strains (360), mined from previous Hsp90 inhibitor yeast screens and heat shock protein interaction data, were screened for differential sensitivities to known N-terminal ATP site-directed Hsp90 inhibitors to reveal f...

Abstract: PURPOSE:To prepare a novel analogous substance of macbecin showing activity against Gram-positive bacteria, fungi, and protozoa, by cultivating a specific ray fungus belonging to the genus Actinosynnema in a proper medium. CONSTITUTION:A ray fungus belonging to the genus Actinosynnema, capable of producing antibiotic C-33196E-4, antibiotic C-33196E-4-R, 18-0- or 21-0-demethylmacbecinIand/or 18-0- or 21-0-dimethylbacbecin II, is cultivated in a proper medium, so that an aitibiotic having activity against Gram-positive bacteria, fungi, or protozoa is accumulated in the medium, and the compound is collected from the culture conventionally, to give the above-mentioned novel anologous substance of macbecin. The ray fungus C-33196 strain is accepted as IFO 14127 by Fermentation Laboratory and FERM P-6138 by Fermentation Research Institute.

Abstract: NEW MATERIAL:The compound of formulaI(one of R1-R3 is H and the others are CH3; X is group of formula II or formula III). USE:It has antibacterial, antimycotic and antiprotozoal activities and is expected to have antitumor activity. PROCESS:The compound of formulaIcan be prepared by contacting the compound of formula IV (i.e. macbecinIor macbecin II) with the cultured product (or its treated product) of microorganisms belonging to Streptomyces genus or Nocardia genus and capable of converting the 17-, 18- or 21-methoxy group of said compound to hydroxyl group, at 6-9pH and 24-40 deg.C for 16-72hr. The microorganism is, e.g. Streptomyces platensis IFO 12901 (ATCC 23948=13865), Nocardia mediterranei ATCC 13685 (IFO 13415), etc.