Studies On The Secondary Metabolites Of Hippospongia Lachne And Their In Vitro Bioactivities

The marine sponge Hippospongia lachne belongs to class Demospongiae,order Dictyceratida and family Spongiidae and genus Hippospongia.Sponges of the genus Hippospongia are rich in secondary metabolites which mainly comprise terpenoids,fats,sterides,and polyketides.Many of the secondary metabolites show various and potent biological activities,including anti-tumor,anti-microbial,anti-malarial,inhibiting DNA polymerase β,and HIV reverse transcriptase activities.48 compounds were isolated from the ethanol extraction of the marine sponge Hippospongia lachne by using various of chromatography methods.They were identified by 1H NMR,13C NMR,HSQC,HMBC,1H-1H COSY,NOESY,MS spectrums,single-crystal X-ray diffraction analysis,time-dependent density functional theory(TDDFT)/ECD calculation and comparison spectroscopic data with literature properties as:1-methyl-5[(3E,7E)-4,8,12-trimethyl-3,7,11-tridecatrien-1-yl]-3-sulfomethyl-pyridinium inner salt(1),1-methyl-5-[(3E)-4-methyl-6-(2,6,6-trimethyl-1-cyclohexen-1-yl)-3-hexen-1-yl]-3sulfomethyl-pyridinium inner salt(2),1-methyl-5-[(3E,7E)-4,8,12-trimethyl-3,7,11tridecatrien-1-yl]-pyridinium-3-carboxylate(3),3-[(3E,7E)-4,8,12-trimethyltrideca-3,7,11-trien-1-yl]-pyridine(4),hipposponlachnin A(5),hipposponlachnin B(6),(-)-hippolide J(7),(+)-hippolide J(8),(5R*)-dihydro-5-[(1R*,4E)-1-hydroxy-1,5,9-trimethyl-4,8-decadien-1-yl]-2(3H)-furanone(9),(5R*)-dihydro-5[(1S*,4E)-1-hydroxy-1,5,9-trimethyl-4,8-decadien-1-yl]-2(3H)-furanone(10),(5R*)-dihydro-5-[(1S*)-1-hydroxy-1-methyl-3-(2,6,6-trimethyl-1-cyclohexen-3-one-1yl)-propyl]-2(3H)-furanone(11),(5R*)-dihydro-5-[(1R*)-1-hydroxy-1-methyl-3-(2,6,6trimethyl-1-cyclohexen-3-one-1-yl)-propyl]-2(3H)-furanone(12),(5R*)-dihydro-5-[(1S*,4E)-1,9-dihydroxy-1,5-dimethyl-4-decaene-8-one-1-yl]-2(3H)-furanone(13),(5R*)dihydro-5-[(1S*,4E)-1,8-dihydroxy-1,5,9-trimethyl-4,9-decadien-1-yl]-2(3H)-furanone(14),(5R*)-dihydro-5-[(1S*,4E)-1,9-dihydroxy-1,5,9-trimethyl-4,7-decadien-1-yl]-2(3H)furanone(15),(5R*)-dihydro-5-[(1S*,4E)-1,8,9-trihydroxy-1,5,9-trimethyl-4-decaene-1yl]-2(3H)-furanone(16),(5R*)-dihydro-5-[(1S*,4E)-1,8,9-trihydroxy-1,5,9-trimethyl-4decaene-1-yl]-2(3H)-furanone(17),(5R*)-dihydro-5-[(1S*)-1,4dihydroxy-1,9-dimethyl5-methylene-4-decaene-1-yl]-2(3H)-furanone(18),(5R*)-dihydro-5-[(1S*)-1,4 dihydroxy-1,9-dimethyl-5-methylene-4-decaene-1-yl]-2(3H)-furanone(19),(5R*)dihydro-5-[(1S*)-1,4,5-trihydroxy-1,5,9-trimethyl-8-decaene-1-yl]-2(3H)-furanone(20),(5R*)-dihydro-5-[(1S*)-1,4,5-trihydroxy-1,5,9-trimethyl-8-decaene-1-yl]-2(3H)-furanone(21),(5R*)-dihydro-5-[(1S*,4E)-1,4,5-trihydroxy-1,5,9-trimethyl-9-decaene-1-yl]-2(3H)furanone(22),(4R*)-5-[(1S*,E)-1-hydroxy-1,5,9-trimethyl-4,8-decadien-1-yl]-2pyrrolidinone(23),(4 R*)-5-[(1R*,E)-1-hydroxy-1,5,9-trimethyl-4,8-decadien-1-yl]-2pyrrolidinone(24),(4Z)-4,6-diethyl-3,6-dihydroxy-8-methyl-4-dodecenoic acid methyl ester(25),4-(2-hydroxy-14-methyl-hexadecyl)-2(5H)-furanone(26),4(2-hydroxy-16-methyl-heptadecyl)-2(5H)-furanone(27),4-(2-hydroxy-octadecyl)-2(5H)furanone(28),4-(2-hydroxy-16-methyl-octadecyl)-2(5H)-furanone(29),3β,5α,6β-trihydroxy-11-formamido-9,11-secocholest-7,11-dien-9-one(30),3β,5α,6β,11-tetrahydroxy-11-oxo-9,11-secocholest-7-en-9-one(31),(6E)-neomanoalide(32),luffariolide C(33),(6Z)-neomanoalide(34),hippolide D(35),(3aS,4R,7aS)-2,3,5,7a-tetrahydro-4-hydroxy-2-oxo-7-[(3E,7E)-4,8,12-trimethyl-3,7,11-tridecatrien-1-yl]3a(4H)-benzofurancarboxamide(36),(1R*,2E,4R*,7E,10S*,11S*,12R*)-10,18-diacetoxydolabella-2,7-dien-6-one(37),simplexolide A(38),simplexolide B(39),simplexolide E(40),woodylide A(41),lemnabourside(42),(3β,5α,6β)-3,5,6-triol-cholest-7-ene(43),(3β,5α,6β,22E)-3,5,6-triolergosta-7,22-diene(44),(3β,5α,6β,22E,24S)-3,5,6-triol-stigmasta-7,22-diene(45),(3β,5α,6β,22E,24R)-3,5,6-triol-stigmasta-7,22-diene(46),3β,5α,6β,11-tetrahydroxy-9,11-secocholest-7-en-9-one(aplidiasterol B)(47),cyclo-(L-leucyl-L-proline)(48).These compounds include thirty terpenoids,five polyketides,four long chain fats,seven sterides,one glucoside,and one cyclic dipeptide.Among these compounds,1-31 were new ompounds.Compounds 5 and 6 possessed a rare 5/6/4/5 fused tetracyclic ring skeleton and may be formed from 37 via an intramolecular[2+2]cycloaddition reaction.Compounds 7 and 8 possessed a unusual bicyclo[4.2.0]octene core.Compounds 5 and 6 were evlatued for anti-allergic activity.Compounds 5 and 6 exhibited higher activity(IC50 49.37 and 23.91 μM,respectively)in the release of β-hexosaminidase inhibition,compared with the market-available anti-asthmatic drug,ketotifen fumarate(IC50=63.88 μM).In addition,5 and 6 suppressed IL-4 production in a dose-dependent manner and significantly inhibited LTB4 release in activated RBL-2H3 cells compared with untreated control.The cytotoxic activities of eighteen compounds(1,5,6,8,17,31-34,36,37,39,41-46)were evaluated against three cancer cell lines,and only compound 39 showed potent cytotoxicties against PC9 and MCF-7 cells with IC50 of 3.54 and 18.01 μM.Compounds 1-4 were further tested for their effects on lymphocyte proliferation and all were inactive.