Re-study On Chemical Constituents And Bioactivities Of The Gorgonian Muriceides Collaris

A gorgonian, commonly known as sea fan or sea whip, is a sessile animal of theSubclass Alcyonaria, Class Anthozoa, Phylum Coelenterata, found throughout theoceans of the world. There are45species from seven families of gorgonians in China,mainly located in Guangdong, Hainan, Zhejiang and Taiwan coast. The South ChinaSea contains plentiful of marine organisms, notably gorgonians. The gorgonianMuriceides collaris with beautiful sky-blue, were collected from the coast ofWeizhou Island, Guangxi province, Sourth China Sea in October,2010. At present,there were few reports on the chemical constituents of Muriceides collaris. In ourongoing program to search for natural products with unique structural features andpronounced biological activities, we have performed a systematic investigation on thechemical constituents and biological activities of the gorgonian Muriceides collarisagain on the basis of the first study on this species of gorgonians by a postgraduatestudent Xuefeng Shi of the class of2010..Isolation and structure determination: Monitoring by bioassay-guidedisolation, the MeOH extract of the gorgonian Muriceides collaris waschromatographed on TLC, silica gel, Sephadex LH-20and semi-preparative HPLC,respectively. Then thirty-seven compounds were isolated and purified from thegorgonian Muriceides collaris. Thirty-six compounds were identified on the basis ofspectral methods (IR, MS, NMR, NMR, CD and caculated ECD etc.) and theirphysicochemical properties. Among them, there were nineteen new compounds andeight compounds with novel skeleton (as new compounds). There were twelveindene sesquiterpenes, collarone A (1),(±)-anthogorgiene A (2),(±)-collarone B (3),(±)-collarone C(4),(±)-collarone D(5),(±)-collarone E (6),5-isopropyl-3,7-dimethyl-1H-indene-1-one (13), amoung them compounds (±)-anthogorgiene A (2),(±)-collarone B (3),(±)-collarone C (4),(±)-collarone D (5) and (±)-collarone E (6)were further purified by chiral separation to obtain (+)-2and ()-2,(+)-3and ()-3,(+)-4and ()-4,(+)-5and ()-5,(+)-6and ()-6; five guaiazulenesesquiterpene alkaloids, collarin A (7),(±)-collarin B (8) and (±)-collarin C (9), amoung them compounds (±)-collarin B (8) and (±)-collarin C (9) were furtherpurified by chiral separation to obtain (+)-8and ()-8,(+)-9and ()-9; fourdimers of sesquiterpene,(±)-collarene A (10),1,1’-biguaiazulene (21) and1,2’-biguaiazulene (22), amoung them compound (±)-collarene A (10) was furtherpurified by chiral separation to obtain (+)-10and ()-10; one liner diterpene lactone,collarone F (11); two cyclopentenone derivatives,(±)-sinularone C (12), which wasfurther purified by chiral separation to obtain (+)-12and ()-12; seven guaianesesquiterpenes,3-formyl-5-isopropyl-8-methylazulene (14),1-methoxylguaiazulene(15), guaiazulene-1,7-dione (16),1-formylguaiazulene (17), guaiazulene (18),sesquiterpene ketolactone (19) and guaianediol (20); one benzene derivative,p-hydroxybenzaldehyde (23); three nucleosides, deoxyadenosine (24), deoxyuridine(25), deoxythymidine (26); one pyrimidine, uracil (27). Among them, compounds1~12、21~23were isolated from the gorgonian M. collaris for the first time..Biological activities: Most pure compounds were evaluated for theircytotoxicities against K562(chronic myelogenous leukemia cell lines of the original),HeLa (human cervical carcinoma cells), HL-60(human leukemia cells) and A549(human lung cancer cells) cancer cell lines by the MTT or SRB method withdoxorubicin for the positive control. The results show that compound7showed strongcytotoxic activity against K562cell lines with IC50values of8.37μΜ. Compound()-8showed strong cytotoxic activity against HL-60cell lines with IC50values of5.08μΜ. Compound11showed strong cytotoxic activity against HeLa cell lineswith IC50values of5.25μΜ. Some pure compounds were evaluated for the antiviralactivity by CPE and MTT methods with ribavirin as positive control. The resultsindicated that compound (+)-5showed moderate antiviral activity. Compounds (+)-2and ()-6showed weak antiviral activity.Moreover, possible biosynthetic pathways of indene sesquiterpenes (1~6，13) andguaiazulene sesquiterpene alkaloids (7~9) were postulated according to theirstructures and literatures, repectively.