Chemical Constituents Of Sponge Dysidea Sp. And Its Symbiotic Aspergillus Flavipes 164013 And Their Bioactivities

Sponge is rich in species and widely distributed all over the world,and it is also considered as the oldest invertebrates.Its own chemical defense system and surface symbiotic microorganisms play an important role in dealing with complex biological environment and fierce competition in the ocean.A sponge identified as Dysidea sp.and its symbiotic fungus Aspergillus flavipes 164013 were selected as the research objects.Then they were extracted by methanol and the extracts were subjected to systematic isolation using silica gel column chromatography,sephadex LH-20 column chromatography,high performance liquid chromatography,reversed phase column chromatography and other modern separation technology methods to yield 28 compounds.Their structures were elucidated by ESIMS,NMR,UV,IR,X-ray diffraction and other spectrographic methods,including 15 sesquiterpene quinones,4 diphenyl ethers,5 alkaloids and 4 others.They are determined as dysideanone F(1),dysideanone G(2),dysiherbol D(3),dysiherbol E(4),Compound A5(5),dysiherbol B(6),dysideanone A(7),dysideanone C(8),avarol(9),dysiquinol A(10),dysiquinol B(11),yahazunol B(12),neoavarol(13),neoavarone(14),avarone(15),isobromolaurenisol(16),dibutyl phthalate(17),methyl linoleate(18),hydroxydihydrobovolide(5-hydroxyl-3,4-dimethy-5-penty-12(5H)-furanone(19),4(2’-hydroxybenzyl)-2-methyl-2H-pyrazino[2,1-b]quinazoline-1,3,6-trione(20),dichloro derivative(21),asterric acid(22),monochloro derivative(23),geodin(24),benzomalvin B(25),benzomalvin E(26),(-)benzomalvin E(27),benzomalvin C(28).Among them,1-5 and 20 are new compounds.All compounds were evaluated for their activity against S.aureus,B.mycoides,M.smegmatis,C.albicans and E,coli.The results showed that 8 showed inhibitory activity against S.aureus and B.mycoides,with MIC values were 4 μg/mL,and 3 showed weak inhibitory activity on B.mycoides,with MIC value were 64 μg/mL,while that of vancomycin,as a positive control was 1 μg/mL.In the preliminary screening of inducing autophagy of U20s cells,it was found that 1 and 4 showed autophagy at a concentration of 20 μM.Among them,1 can increase the autophagy level of U20s,while 4 blocked its autophagy,8 and 9 have cytotoxic activity at the concentration of 20 μM,which need to be retested under low concentration.