摘要
海洋生物中的海绵(marine sponge)属于多孔动物门(Porifera),是最原始的低等多细胞海洋动物。研究发现,海绵次生代谢产物具有显著的生物活性,涉及到抗菌、抗肿瘤(细胞毒性)、抗真菌、抗病毒(包括抗HIV)、抗炎、心血管等各个方面,尤其是细胞毒性化合物超10%,显著高于其他海洋动物(2%),陆生植物(<1%)或微生物(<1%)。
为了进一步从海洋生物中寻找新的生物活性成分,本文对采自中国南海三亚附近海域的两种海绵样品Xestospongia testudinaria和Spheciospongia sp.进行了比较系统的化学成分和体外生物活性筛选研究。从海绵Xestospongia testudinaria乙酸乙酯提取物中,运用多种色谱方法,共分离得到29个化合物;从海绵Spheciospongia sp.石油醚和乙酸乙酯提取物中,运用多种色谱方法,共分离得到20个化合物。利用核磁共振(NMR)、质谱(MS)、红外(IR)、圆二色谱(CD)等现代波谱技术确定了它们的结构,其中新化合物24个。
从海绵Xestospongia testudinaria中,共分离鉴定了29个化合物,分别为:testudinlide A(1)、testudinlide B(2)、testudinlide C(3)、testudinlide D(4)、testudinlideE(5)、testudinlide F(6)、testudinlide G(7)、testudinlide H(8)、testudinlide I(9)、testudinlide J(10)、testudinlide K(11)、testudinlide L(12)、testudinlide M(13)、testudinlide N(14)、testudinlide O(15)、testudinlide P(16)、testudinlide Q(17)、testudinlide R(18)、testudinlide S(19)、testudinlide T(20)、testudinlide U(21)、testudinlide V(22)、(7E 13E,15Z)-14,16-dibromo-hexadeca-7,13,15-trien-5-yonicacid(23)、(7E,13E,1 5Z)-14,16-dibromo-hexadeca-7,13,15-trien-5-yonic ethylester(24)、3-吲哚甲醛(25)、3-吲哚甲酸(26)、3-吲哚甲酸乙酯(27)、环(异亮-缬)二肽(28)、环(亮-缬)二肽(29)。化合物1-22为新化合物。对部分特征性代谢产物1-23进行了初步的体外抑制肿瘤细胞和HIV-1病毒感染细胞的生长抑制活性,结果均未显示明显的生物活性。
从海绵Spheciospongia sp.中,共分离鉴定了20个化合物,分别为:spheciospongone A(30)、spheciospongone B(31)、蚱蜢酮(32)、3β-hydroxy-5α,6α-epoxy-7-megastigmene-9-one(33)、黑麦草内酯(34)、胆甾醇(35)、胆甾-4-稀-3-酮(36)、胆甾-3,6-二酮(37)、3β-羟基-胆甾-5-稀-7-酮(38)、6β-羟基-胆甾-4-稀-3-酮(39)、胆甾-4-烯-3,6-二酮(40)、胆甾-5-烯-3-酮(41)、胆甾-3β,5α,6β-三醇(42)、6-甲氧基-胆甾-3β,5α-二醇(43)、5-甲氧基-胆甾-3β,6β-二醇(44)、3-吲哚乙酰胺(45)、苯乙酰胺(46)、胸腺嘧啶脱氧核苷(47)、N-甲基-尿嘧啶核苷(48)、2'-脱氧鸟嘌呤核苷(49)。化合物30、31为新化合物。对部分化合物进行了初步的抗肿瘤细胞的细胞毒活性筛选,甾体类化合物42显示出一定的人结肠腺癌(REH)细胞株抑制活性。
该研究丰富和发展了南海海绵Xestospongia testudinaria和Spheciospongia sp.的化学成分研究,为海洋天然产物的药理筛选提供了多样性结构,并为化学分类学研究提供依据,丰富了我国南海海绵代谢产物的研究内容。
Marine sponge,which belongs to Porifera,is the most original multicellular marine organism.A great deal of research works on marine sponges revealed that the secondary metabolites of marine sponge possess remarkable biological activities,such as anti-bacterial,anti-tumor(cytotoxic),anti-fungus,anti-virus,anti-inflammation activities,and so on.
In order to find natural products with the unique structures and promissing biological activities,two species sponges Xestospongia testudinaria and Spheciospongia sp.were collected from South China Sea near Sanya,Hainan province.Various of chromatography techniques were performed during the isolation and purification of the EtOAc extracts of Xestospongia testudinaria,as well as the PE and EtOAc extracts of sample of Spheciospongia sp.29 compounds were obtained from X.testudinaria and 22 compounds were isolated from Spheciospongia sp.Their structures were determined by extensive spectroscopic analysis in association with physical and chemical properties,as well as comparison of their spectral data with those reported in literatures.
29 compounds isolated from the marine sponge Xestospongia testudinaria were identified as testudinlide A(1),testudinlide B(2),testudinlide C(3),testudinlide D(4), testudinlide E(5),testudinlide F(6),testudinlide G(7),testudinlide H(8),testudinlide I(9),testudinlide J(10),testudinlide K(11),testudinlide L(12),testudinlide M(13), testudinlide N(14),testudinlide O(15),testudinlide P(16),testudinlide Q(17), testudinlide R(18),testudinlide S(19),testudinlide Y(20),testudinlide U(21), testudinlide V(22),(7E,13E,15Z)- 14,16-dibromo-hexadeca-7,13,15-trien-5-yonic acid(23),(7E,13E,15Z)-14,16-dibromo-hexadeca-7,13,15-trien-5-yonic ethyl ester(24),indole-3-carboxaldehyde(25),indole-3-carboxylic acid(26), ethyl-indole-3- carboxylate(27),cyclo-(Ile-val)(28),cyclo-(Leu-val)(29) respectively.Among them,compounds 1-22 were new compounds.Compounds 1-23 were screend for their anti-tumor grouth and anti-HIV activities,however,they also showed unsignificant activity.
20 compounds isolated from the marine sponge Spheciospongia sp.were identified as spheciospongone A(30),spheciospongone B(31),grasshopper ketone (32),3β-hydroxy-Sα,6α-epoxy-7-megastigmene-9-one(33),loliolide(34),cholesterol (35),cholest-4-en-3-one(36),cholest-3,6-dione(37),3β-hydroxy-cholest-5-en-7-one (38),6β-hydroxy-cholest-4-en-3-one(39),cholest-4-en-3,6-dione(40),cholest-5-en -3-one(41),cholest-3β,5α,6β-triol(42),6-methoxy-cholest-3β,5α-diol(43), 5-methoxy-cholest-3β,6β-diol(44),indole-3-acetamide(45),benzene acetamide(46), thymidine(47),uridine-N-methyl(48),2'-deoxyguanosine(49) respectively.Among them,compounds 30,31 were new compounds.On the base of anti-tumor bioactive screening,Compound 42 showed significant growth inhibitiory activity on REH cell line.
This research work enriched the chemical constituents from marine sponge Xestospongia testudinaria and Spheciospongia sp.,and expanded the spectroscopy technique for structure elucidation of marine natural products,also enriched the chemical deversity for Chinese marine sponges.
引文
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