Studies On Secondary Metabolites Of Haliclona Baeri

The sponge Haliclona baeri belongs to the family Chalinidae,order Haplosclerida,class Demospongiae.According to the records of Wo RMS（World Rigister of Marine Species）,there are 9 subgenera,including more than 700 species of the genus Haliclona in the world,H.viscosa,H.crassiloba and H.cymaeformis were mainly studied.Up to now,more than 260 secondary metabolites had been isolated from the genus Haliclona,including alkaloids,steroids,alkynes,terpenoids,glycosphingolipids,peptides and other compounds,most of which showed antibacterial,cytotoxic and enzyme inhibition activities,etc..Since only two papers about the secondary metabolites of the sponge H.baeri had been reported,we investigated the chemical constituents of the sponge H.baeri systematically,which was collected from Xuwen County,Zhanjiang City,Guangdong Province.The sponge H.baeri was extracted by 95%ethanol in room temperature and suspended in H₂O,which was partitioned with ethyl acetate and n-butanol,respectively.The two extracts were isolated by various chromatographic separation techniques,such as silica gel,Sephadex LH-20and HPLC to obtain 37 compounds.The structures of these compounds with absolute configurations were identified by modern spectroscopic techniques（NMR,MS,IR,UV,etc.）,ECD calculation and comparing specific optical rotations with those reported in literatures as halicline A（H1）,halicline B（H2）,cyclo（Gly-L-Pro）（H3）,cyclo（S-Pro-6-hydroxyl-S-Ile）（H4）,cyclo（L-Pro-L-Leu）（H5）,（3S,8a S）-hexahydro-3-[（1R）-1-hydroxyethyl]pyrrolo[1,2-a]pyrazine-1,4-dione（H6）,soboliferamide（H7）,cyclo（L-Pro-L-Ser）（H8）,cyclo（L-Pro-L-Tyr）（H9）,callysponine（H10）,24-isopropylcholesterol（H11）,3β-sitosterol（H12）,1,2-diazinan-3-one（H13）,（S）-3-hydroxypiperidin-2-one（H14）,（+）-1,2,3,4-tetrahydro-4-hydroxy-4-quinolinecarboxylic acid（H15）,N-acetyl-L-phenylalanine 2-hydroxyethyl ester（H16）,N-acetyl-L-phenylalanine（H17）,N-acetyl-L-tyrosine methyl ester（H18）,1H-indole-3-aldehyde（H19）,3-carboxylpyridine（H20）,phenylamide（H21）,N-2-phenethylacetamide（H22）,p-hydroxybenzoic acid（H23）,p-Hydroxybenzaldehyde（H24）,ethyl（αR）-α,4-dihydroxybenzeneacetate（H25）,phenylacetic acid（H26）,loliolide（H27）,chakyunglupulin B（H28）,5-methyluracil（H29）,2,4-pyrimidinediol（H30）,uracil glucoside（H31）,2’-O-methyluridine（H32）,thymidine（H33）,2’-deoxyuridine（H34）,1-（β-D-ribofuranosyl）-1H-1,2,4-triazone（H35）,β-adenosine（H36）and（9Z）-octadecenamide（H37）.Compounds H1 and H2 were two new 2,5-dioxopiperazines.Compound H1 represented the first example of natural 2,5-dioxopiperazine bearing a L-azetidine-2-carboxylic acid moiety.Compounds H3,H6-H8,H10,H11,H13-H22,H25-H28,H32,H35 and H36 were isolated from this genus for the first time.In addition,the anti-inflammatory,cytotoxic and antibacterial activities of H1-H18 and H27-H36 were tested,which showed that the new compounds H1 and H2 had weak inhibitory activities against NF-κB with IC₅₀values of 58.9 and 82.9μM,respectively.Compound H2 has weak cytotoxic activity against K562 cell line with IC₅₀value of 72.9μM.Compounds H1 and H2 had weak inhibitory activity against Enterococcus faecalis ATCC29212 with MIC value of128.0μM.The other tested compounds have no obvious anti-inflammatory,cytotoxic and antibacterial activities.