Studies on the Chemical Constituents and Bioactivities of Artabotrys uncinatus and Cananga odorata and Development of New Drugs of Sterols
| Autor: | Tian-Jye Hsieh, 謝天傑 |
|---|---|
| Rok vydání: | 2003 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 91 As a result of our continuing search for bioactive agents (e.g. antiplatelet aggregation, antitumor and anti-HIV agents) from Formosan Annonaceous plants, we have undertaken the methanolic extracts of the fruits, roots stems and leaves of Artabotrys uncinatus and the methanolic extracts of the fruits and leaves of Cananga odorata for evaluation of their in vitro antitumor activity. Sixty-four compounds, including thirty-two alkaloids, two triterpenoids, ten steroids,nine flavonoids, four benzenoids, one lactam, one cyclohex-2-en-1-one, one neolignan, and three lignans, were isolated from A. uncinatus and their structures were established on the basis of NMR and MS data interpretation. Among them, artabonatine -C (84), -D (85), A (86), -E (87), -F (88), -B (97), and uncinine (124) were new compounds. We have also isolated twenty-two compounds, including thirteen alkaloids, three sesquiterpenes, one guaipyridine sesquiterpene alkaloid, one benzenoid,two steroids, one cyclohexane and two amides from C. odorata. Of these compounds, four new compounds, (+)-ushinsunine--N-oxide (125), cananodine (128), cryptomeridiol-11--L-rhamnoside (129) and -eudesmol-11--L-rhamnoside (130) were characterized by spectral and chemical transformation studies. Since steroids and triterpenes have shown anti-cancer and anti-HIV activity, we synthesized a series of derivatives for bioactivity testing. In previous studies, butenolides revealed anti-cancer activity. As a result, we synthesized several butenolide analogues for screening of antitumor activity. At a concentration of 100 g/mL, quercetin (51) showed significant inhibition of arachidonic acid (AA)-induced and collagen-induced platelet aggregation；7-dehydrocholesteryl succinic acid (155) showed significant inhibition of collagen-induced platelet aggregation. Furthermore, atherospermidine (2), lysicamine (3), polycarpol (33), squamolone (101), 6-hydroxystigmasterone (106), stigmast-4-en-3,6-dione (107), stigmast-4,22-dien-3,6-dione (108), squamolone (101), blumenol A (115), (+)-syringaresinol (117), (+)-ushinsunine--N-oxide (125), cananodine (128), cryptomeridiol 11--L-rhamnoside (129), -eudesmol (131), N-trans-feruloytranine (134), cleistopholine (136) and stigmast-5,22-dien-3-one (139) were found to exhibit significant cytotoxicity against two human hepatocarcinoma cell lines (Hep G2 and 2,2,15). On antitumor bioassay, stigmast-4,22-dien-3,6-dione (108) showed significant cytotoxicities against HONE-1 and NUGC cell lines at (50μg/mL). Liriodenine (1), atherspermidine (2), luteolin (112) showed marginal cytotoxic activity against the HONE-1 and NUGC cell lines (50μg/mL). Derivatives of sterols such as -sitosterylglycoside (49), 6-hydroxystigmasterone (140), 6-succinicylstigmasterone (153), and 7-dehydrocholesterol (154) showed inhibition of HIV. Using a fermentation technique, Saccharomyces cerevisiae produced two cytotoxic alkaloids liriodenine (1) and (-)-ushinsunine--N-oxide (63) by using 14 as precursor. Although compounds 1 and 63 have been synthesized from 14 by chemical oxidation and isolated from C. odorata, we proved the oxidative conversion of alkaloid in the microorganic system. As a result, the isolation and synthesis of compounds and the bioactivities can be provided for further studies. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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