| In recent years, because of the appearances of multi-drug resistance in tumor cells, the therapeutical efficacy of anticancer drugs was severely limited. It is very difficult to find new anticancer compounds from terraneous organisms. So the ocean has attracted extensive attention worldwide.71% of the earth’s surface is covered by oceans, in which microorganism resources are very abundant. The special environment of the ocean make marine microorganism diversity, of which secondary metabolites have special structures and potent activities. It affords big resources for people to search new anticancer compounds.Through bioactive assays,14 marine-derived microorganism strains were selected for further TLC screening.4 strains with various and plentiful metabolites were fermented on a large scale. The secondary metabolites of three fungus strains and one bacterial strain were isolated systematically, and their chemical structures and antitumor activities were investigated.By means of various isolation methods such as recrystallization, opening silica gel, Sephadex LH-20, ODS column chromatography, preparative TLC, MPLC and HPLC, the chemical constituents of the fermentation broth and mycelium of these four strains were isolated.26 compounds were isolated from strain G25-20 (Hypocrea virens) which was separated from the true mangrove flora Rhizophora apiculata in the mesolittoral zone of Shatian county, Guangxi province, China, and their structures were determined by means of physicochemical properties and spectral methods. They were identified as 2-methylimidazo[1,5-b]isoquinoline-1,3,5(2H)-trione (1), isolumichrome (2), 1-acetyl-β-carbolin (3), (22E,24R)-ergosta-5,7,22-triene-3β-ol (4), (22E,24R)-ergosta-8,22-diene-3β,5α,6β,7α-tetraol (5),5α,9α-epidioxy-(22E, 24R)-ergosta-7,22-diene-3β,6β-diol (6),5α,8α-epidioxy-(22E,24R)-ergosta-6, 22-dien-3β-ol (7), (22E)-ergosta-7,22-diene-3β, 5α,6β-triol (8),3β,5α,9α-trihydroxy-(22E,24R)-ergosta-7,22-diene-6-one (9),1 (10→6)abeo-(22E,24R)-ergosta-5,7,9,22-tetraene-3α, 11α-diol (10),3β-hydroxy-cholesta-5-ene (11),24- methylene lanostane-8-ene-3β-ol (12), benzothiazoline-2-thione (13),2,2’-dibenzothiazolyl disulfide (14), gliotoxin (15), bisdethiobis-(methylthio)gliotoxin (16), pyrrolopiperazine-2,5-dione (17),3-isobutyl-8-hydroxypyrrolopiperazine-2,5-dione (18),3-benzylpiperazine-2,5-dione (19),3-benzyl-8-hydroxypyrrolopiperazine-2, 5-dione (20),5-hydroxy-3-hydroxymethyl-2-methyl-7-methoxychromone (21), adenosine (22),2-acetamido-2-deoxy-α-D-glucopyranose (23),3S*,4R*-dihydroxy-3-methylpentan-2-one (24),3R*,4R*-dihydroxy-3-methylpentan-2-one (25), and 6-methylbenzene-1,2,4-triol (26).11 compounds were isolated from strain Z14-22 (Bacillus subtilis) which was separated from the mangrove flora Acanthus ebrectearas in the mesolittoral zone of the South China Sea. Their structures were identified as 3-benzyl-6-isopropylpiperazine-2,5-dione (27),3-isobutylpyrrolo piperazine-2, 5-dione (28),3-benzylpyrrolopiperazine-2,5-dione (29),3-methyl-8-hydroxy pyrrolopiperazine-2,5-dione (30),3-hydroxymethylpyrrolopiperazine-2,5-dione (31), thymine (32), uracil (33), dihydrothymine (34), hydrocinnamic acid (35), 3-isobutyl-8-hydroxypyrrolopiperazine-2,5-dione (18), and 3-benzylpiperazine-2, 5-dione (19).15 compounds were isolated from strain Z23-28 (Fusarium sp.) which was separated from the true mangrove flora Rhizophora apiculata in the mesolittoral zone of the South China Sea. They were identified as 1,3,5-trihydroxy-7-methylanthraquinone (36), citreorosein (37),3β,15-dihydroxyl-(22E,24R)-ergosta-5, 8(14),22-triene-7-one (38), 3-O-β-D-glucopyranosyl-stigmasta-5,24(28)Z-diene (39), uridine (40), inosine (41),3-isopropylpyrrolopiperazine-2,5-dione (42),10S-hydroxyoctadecanoic acid (43), mannitol (44), amber acid (45),5α,8α-epidioxy-(22E, 24R)-ergosta-6,22-dien-3β-ol (7), (22E,24R)-ergosta-7,22-diene-3β,5α,6β-triol (8), 3β,5α,9α-trihydroxy-(22E,24R)-ergosta-7,22-diene-6-one (9), pyrrolopiperazine-2, 5-dione (17), and uracil (33).12 compounds were isolated from strain GT-308 (Penicillium sacculum) which was separated from the halophyte Atriplex sp. in the mesolittoral zone of Dongying city, Shandong province, China. These 12 compounds were identified as 1-hydroxy-3-methoxy-6-sulfo-8-methylxanthone (46) 1,6-dihydroxy-3-methoxy-8-methylxanthone (47), 1-hydroxy-3-methylxanthone (48), 3S-methyl-4,5-dihydroxy-6-methoxyisobenzofuran (49), griseofulvin (50),1,8- dihydroxy-3-methylanthraquinone (51), citreoanthrasteroid B (52), griseophenone B (53), griseophenone C (54), (22E,24R)-ergosta-5,7,22-triene-3β-ol (4), thymine (32), and 1,3,5-trihydroxy-7-methylanthraquinone (36).66 compounds had been isolated from the fermentation broth and mycelia of four marine-derived microorganism strains. Among them, the structures of 54 compounds were elucidated on the basis of physicochemical properties and spectroscopic data. Compounds 1 and 46 were two new compounds.The antitumor activities of some secondary metabolites isolated from the fermentation broth and mycelium of these four strains were tested. It was found that compounds 5,15,21 and 49 showed more potent growth inhibitory activities against human leukemia HL-60 cells with IG50 values of 8.86,< 0.1,14.29,8.46μM, respectively. Compound 15 also showed potent growth inhibitory activities against human prostate cancer PC-3 cells and human breast cancer MCF-7 cells with IG50 values of 0.15 and 0.12μM.The research progress on steroids from marine-derived organism were reviewed based on the literatures. |
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