期刊
PLANTA MEDICA
卷 77, 期 17, 页码 1932-1938出版社
GEORG THIEME VERLAG KG
DOI: 10.1055/s-0030-1271199
关键词
phenanthroindolizidine; septicine; Tylophora ovate; Asclepiadaceae; tylophorine; tylophovatine
资金
- National Science Council of Taiwan [95-320-B-400-010-MY3, 99-320-B-400-010-MY3]
- National Health Research Institutes, Taiwan [BP-096-PP-05, BP-097-PP-05, BP-098-PP-05]
- National Tsing Hua University
- National Health Research Institutes
An investigation of alkaloids present in the leaves and stems of Tylophora ovata led to the isolation of two new septicine alkaloids and one new phenanthroindolizidine alkaloid, tylophovatines A, B, C (1, 2, and 5), respectively, together with two known septicine and six known phenanthroindolizidine alkaloids. The structures of the new alkaloids 1, 2, and 5 were established by means of spectroscopic analyses. These eleven alkaloids show in vitro anti-inflammatory activities with IC50 values ranging from 84 nM to 20.6 mu M through their suppression of nitric oxide production in RAW264.7 cells stimulated by lipopolysaccharide and interferon-gamma. Moreover, these substances display growth inhibition in HONE-1, NUGC-3, HepG2, SF-268, MCF-7, and NCI-H460 cancer cell lines, with GI(50) values ranging from 4 nM to 24.2 mu M. In addition, tylophovatine C (5) and 13a(S)-(+)-tylophorine (7) were found to exhibit potent in vivo anti-inflammation activities in a rat paw edema model. Finally, structure-activity relationships were probed by using the isolated phenanthroindolizidines and septicines. Phenanthroindolizidines are suggested to be divided into cytotoxic agents (e. g., 10 and 11) and anti-inflammation based anticancer agents (e. g., 5-9).
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