| The increase of bacterial drug resistance poses a great threat to human health and safety.In order to solve this problem,we urgently need to find novel and efficient antibiotics.70%of the antibiotics widely used by human beings are produced by various actinomycetes,and marine actinomycetes are one of the most abundant resources of bioactive substances of marine microorganisms.Due to its special environment,the ocean provides rich resources for the discovery of various active lead compounds.In order to obtain compounds with novel structure and high antibacterial activity from secondary metabolites of marine actinomycetes.In this paper,twelve marine actinomycetes were selected as the research objects.Two strains of secondary metabolites with rich antibacterial activity were screened out by chemical screening and activity screening.Antibacterial activity was oriented.A total of thirty compounds were isolated from these two strains by TLC,silica gel column chromatography,gel column chromatography,and semi preparative HPLC.Then the structures of these compounds were determined by nuclear magnetic resonance(NMR),high resolution mass spectrometry(HR-MS),infrared(IR),ultraviolet(UV),single crystal diffraction(X-ray),optical rotation and other modern spectral analysis techniques.Nineteen compounds were isolated from Nonomuraea sp. MYH522,including one diketopiperazine compound:cyclo-4-OH-pro-Phe(1);Two acid compounds:Pyrole-2-carboxylic acid(2),Brevinic acid(3);Five macrocyclic lactams compounds:Fluvirucin B7(4),Fluvirucin B8(5),Fluvirucin B9(6),Fluvirucin B6(7),Fluvirucin B10(8);Eleven triterpenoids:sayasapocin A-K(9-19),of which compounds(4-6,8-19)are fifteen new compounds.Eleven compounds were isolated from Streptomyces sp. MYH929,including two p-triphenyl O-b-glucuronide compounds:echosides A(21),echosides C(22);One naphthoquinone compound(ansamycin):hygrocins E(20),hygrocins D(23);One phenylethanol compound:Phenethyl alcohol(24);One macrocyclic lactam compound(ansamycin):17-O-demethylgeldanamycin(25);One macrolide compound:oxohygrolidin(26);One macrolide:elaiophylin(27);Two polycyclic polyether compounds:PK955A(28),Nigericin(29);One diterpene compound:streptooctatin B(30).The isolated compounds 4-8 were screened for antimicrobial activities against pathogenic bacteria including Staphylococcus aureus ATCC25923 and Escherichia coli ATCC25929,and Candida albicans(the standard clinical isolated strain SC5314,the fluconazole-resistant clinical isolates of 901 and 904).Compounds 4-8 did not exhibit any activities against S.aureus and E.Coli up to 128μg/m L.Moreover,4-8 were not active against C.albicans SC5314,901,or 904 at 64μg/m L.However,when combined with 8μg/m L of fluconazole,compounds 4,7,8 showed synergistic antifungal activities against fluconazole-resistant isolates of C.albicans 901 and 904 during 24 hours. |