Phytochemicals From Garcinia, Mesua And Jatropha Species And Their Biological Activities

Author

LIM CHAN KIANG

Date

2005

Keyword

Garcinia penangiana, Garcinia nitida, Mesua daphnifolia, Mesua beccariana , Jatropha podagrica, phytochemical investigations, biological activities, cytotoxic assays, cell lines

Abstract

Extensive studies on 5 plants, Garcinia penangiana, Garcinia nitida, Mesua daphnifolia, Mesua beccariana and Jatropha podagrica have resulted in the isolation of twenty one compounds. Out of these compounds two are new.  All these compounds were isolated by means of chromatographic method and their structures derived on the basis of spectroscopic evidence, mainly   ID and   2D NMR spectroscopy. Chemical investigations on the stem bark extracts of Garcinia penangiana yielded a flavonoid, catechin (86) and a steroidal triterpene, stigmasterol (85) whereas the stem bark extracts of Garcinia nitida yielded two triterpenoids, stigmasterol (85) and stigmasterol acetate (87) plus a total of five xanthones, inophyllin B (88), osajaxanthone (89), 13,7-trihydroxy-2,4-bis(3-methylbut-2-enyl)xanthone (90), rubraxanthone (91) and 3-isomangostin (92). Meanwhile, studies on the stem bark extracts of Mesua daphnifolia yielded three triterpenoids, friedelin (93), friedelan-1,3-dione (94) and Iup-20(29)-en-3ß-ol (96), three known xanthones, ananixanthone (95), cudraxanthone G (97) and euxanthone (52) and a new xanthone, daphnifolin (98). On the other hand, the stem bark extracts of Mesua beccariana gave two triterpenoids, stigmasterol (85) and friedelin (93) and a phenylcoumarin, isocalanone (99). Jatropha podagrica afforded two triterpenoids,ß-sitosterol (61) and acetylaleuritolic acid (77), a coumarin, fraxidin (101), a new ferulic acid ester, n-heptyl ferulate (100) and sucrose (102). Acetylation on rubraxanthone (91) gave two new compounds which were never reported before. These are rubraxanthone monoacetate (103) and rubraxanthone diacetate (104). The known rubraxanthone triacetate (105) was also synthesized. Cytotoxic assay was performed using CEM-SS (T-lymphoblastic leukemia) cell line. All the crude extracts of Garcinia penangiana and Jatropha podagrica, the crude hexane extract of Mesua beccariana and the crude hexane and chloroform extracts of Garcinia nitida were found to show significant growth inhibitory activities with IC50 values of less than 30 µg/ml. Cytotoxic assays were also carried out on the pure compounds towards the CEM-SS (T-lymphoblastic leukemia), HeLa (cervical carcinoma), MDA-MB-231 (human estrogen receptor negative breast cancer) and CaOV3 (human ovarian cancer) cell lines. Cudraxanthone G (97) and friedelan-1,3-dione (94) were found to show strong inhibitory activities toward the HeLa cell line with IC50 values of 4.0 and 4.6 µg/ml respectively. Both cudraxanthone G (97) and rubraxanthone (91) gave moderate inhibitory activities with IC50 values of 6.7 and 9.4  µg/ml respectively towards the CEM-SS cell line. The MDA-MB-231 cell line was found to be very susceptible towards most of the prenylated xanthones tested: cudraxanthone G (97) (IC50 =1.3 µg/ml), inophyllin B (88) (IC50 = 1.4 µg/ml), l,3,7-trihydroxy-2,4-bis(3-methylbut-2-enyl)xanthone (90) (IC50 = 2.2 µg/ml) and ananixantone (95) (IC50 = 4.6 µg/ml). Meanwhile, euxanthone (52) gave a moderate activity (IC50 = 9.0 µg/ml) towards the CaOV3 cell line. Most of the compounds tested indicated selective activity towards the cancer cell lines except for cudraxanthone G (97) which was found to have a broad spectrum of activities. Antimicrobial assays were carried out towards four pathogenic bacteria: Methicillin Resistant Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhimurium and Bacillus subtilis. Most of the crude extracts tested against these microbes gave only moderate or weak activities except for the ethyl acetate extract of Jatropha podagrica, which was strongly active against the microbe Pseudomonas aeruginosa  with an inhibition width of 15 mm which is close to that of the standard, streptomycin sulphate (16 mm). Larvicidal tests were carried out against the larvae of Aedes aegypti. The larvae were strongly susceptible to the hexane and chloroform extracts of Mesua daphnifolia with LC50 values of as low as 9.7 and 6.0 ppm respectively while the other crude extracts gave LC50 values of more than 60 ppm. The pure compound, rubraxanthone (91) indicated a strong larvicidal activity with LC50 value of 15.5 ppm. Antifungal assays were also carried out on the crude extracts of Mesua daphnifolia towards the microbes, Candida albican, Aspergillus ochraceaus, Sacchoromyces cerevisiae and Candida lypolytica. All the crude extracts of Mesua daphnifolia exhibited moderate activities towards the microbe Candida lypolytica but they were not active against the other targeted microbes.