Study On Antifungal Secondary Metabolites From Streptomyces Antibioticus H74-21

We obtained a marined-derived and antifugal actinomycete H74-21 by activity screening. H74-21 was fermented on small scale under different culture mediums. Based on the chemical composition analysis and the preliminary screening results of their antifugal activity to choose the optimal medium for fermentation. Various chromatographic(TLC, ODS, silica gel, and Sephadex LH-20 column chromatography, MPLC, HPLC, etc.) and spectroscopic methods(NMR, MS, IR, UV, etc.)coupled with bioassay-guided fractionation were applied for the isolation and structural identification of compounds from the mycelium of Streptomyces sp. H74-21. Twenty-two compounds were isolated from the antifungal strain, including two new compounds(16 and 21) and a new nature product(22). They were identified to be antimycin A1a/1b(1、2), antimycin A7b(3), antimycin A2a(4), antimycin A3a/3b(5、6), antimycin A1a/1b(7、8), cyclo-((S)-Pro-(R)-Leu)(9), seco-((S)-Pro-(R)- Val)(10), cyclo-(S)-Pro-8- hydroxy-(R)-Ile(11), actinomycin D(12), actinomycin X2(13), deisovalerylblastomycin(14), urauchimycin B(15), kitamycin C(16), kitamycin A(17), kitamycin B(18), 2-phenyl-acetamide(19), ergosterol(20),(2S,3R)-LThreonine, N-[3-(formylamino)-2-hydroxybenzoyl]-ethyl ester(21), and 1, 4-dimethyl-3-isopropyl-2,5- piperidinedione(22). Amongst them, compounds 1~8, 12, 13 and 14~18 showed good antifugal activities against Candida albicans and good cytotoxic activities against MCF-7, SF-268, and NCI-H460 cancer cell lines. Moreover, the antifugal MIC values of compounds 1-8 was less than 0.325 ?g/disk, compounds 12 and 13 displayed potent cytotoxic activity with IC50 values less than 1.6 ?g/ml. Strain H74-21 was identified to be a Streptomyces antibioticus strainbased on its 16 S rDNA, as well as morphological characteristics, cultural characteristics, and physiological and biochemical characteristics. Morphological and cultural characteristics: the color of substrate mycelium was brown, and the color of aerial mycelium was gray. In the electron microscope, aerial hyphae formed spores silk, it was straight and cylindrical. Physiological and biochemical characteristics: H74-2 had mild ability to make gelatin liquefaction, strong ability to hydrolyze starch, couldn’t grow on cellulose, couldn’t make milk coagulation or milk peptonization.