Studies On The Chemical Constituents And Bioactivities Of Three Marine Organisms

Coral reefs and mangroves are two major marine ecosystems, rich in variety ofresources. The special habitat lead marine organisms to producing abundantsecondary metabolites with unique structural features and diversity biologicalactivities. In our research for novel natural products with pronounced biologicalactivities from marine organisms, three marine organisms, the soft coralSarcophyton.sp, the mangrove plant Sonneratia paracaseolaris, the marine spongePericharax heteroraphis were collected in the China South Sea. The study includesisolation and structural elucidation of the chemical constituents, and preliminaryevaluation for bioactivities of pure compounds. An extensive chromatographictechniques resulted in the isolation of77compounds from the selected three marineorganisms, and73compounds’ structures were determined on the basis of MS, NMR,IR, UV methods and by comparison with the reported data in literature, including9new ones.By using silica column, Sephadex LH-20, ODS column, HPLC and etc,19purecompounds (SAR1~SAR19) were isolated and determined from the soft coralSarcophyton.sp, including13polyhydroxylated sterols (SAR1~SAR13),3cembranoids (SAR14~SAR16),3ceramides (SAR17~SAR19). SAR1~SAR3were found for the first time; From mangrove plant Sonneratia paracaseolaris,51compounds were isolated, and47compounds were determined.including17triterpenoids (SP-1~SP-17),1phytol (SP-18),7sterols (SP-19~SP-25),2sesquiterpenes (SP-26~SP-27),1fatty acid (SP-28),4lignins (SP-29~SP-32),5flavones (SP-33~SP-37),7benzene derivatives (SP-39~SP-46),1tannin (SP-47),SP-1~4, SP-12were the new compounds. All the compounds were discovered fromSonneratia paracaseolaris for the first time.7compounds (PH-1~PH-5) wereisolated and determined from the sponge Pericharax heteroraphis, including5imidazole alkaloids (PH-1~PH-5),1polyketide (PH-6),1nucleoside (PH-7), except for PH-2, all the compounds were discovered from the genus Pericharax for the firsttime.The cytotoxicities for the polyhydroxylated sterols, triterpenoids, and ligninsagainst tumor cell lines were evaluated in vitro by MTT[3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl-2H-tetrazolium bromide] and SRB(Sulforhodamine B) methods, a series of compounds (SAR1~SAR11, SP-3~4,SP-9, SP-11, SP-14, SP-31) were discovered to have significant cytotoxicities againstselected tumor cell lines. In addition, preliminary structure-activity relationships forthe isolates were discussed. The OAc group at C-11was proposed to be an importantpharmacophore for their cytotoxicities in the3,5,6-triol steroids and the OHsubstitution at C-11could improve the selectivity but decrease activity, which werediscovered for the first time； A preliminary structure activity relationships (SAR)analysis of triterpenoids suggested that introduction of an O-p-coumaroyl group atC-3could increase the cytotoxicities against HeLa, P388and A549cell lines nomatter cis or trans configuration of O-p-coumaroyl and2-OH played significant roleson the cytotoxicities, whereas OH group at C-1and the substituent patterns at C-28showed no effects. Structure activity relationships (SAR) of lignins showed thatmethoxyl was an esssential pharmacophore for their cytotoxicities against HeLa, P388,A549and K562cell lines. Besides the position was also important. Antiviral activitiesof these three kinds of isolates against influenza A H1N1virus (IAV) were alsoevaluated by CPE (the cytopathic effects) assays. Compounds SAR4and SP-1exhibited significant anti-H1N1virus activities with IC50values of19.6and28.4g/mL (Ribavirin as a positive control with IC50value of24.6g/mL), respectively.This is the first discovery for anti-H1N1virus activities of these three kinds ofisolates.In this paper,9metabolites including3polyhydroxylated sterols (SAR1~SAR3),5triterpenoids (SP-1~4, SP-12),1imidazole alkaloid (PH-5), were found for thefirst time. The evaluation of bioactivities led to the discovery of cytotoxic andanti-H1N1virus secondary metabolites and provided meaningful structure activity relationships which may be useful for the research of marine natural products.