Isolation and biological activities of phenanthroindolizidine and septicine alkaloids from the Formosan Tylophora ovata.

Abstract

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 μM through their suppression of nitric oxide production in RAW264.7 cells stimulated by lipopolysaccharide and interferon-γ. Moreover, these substances display growth inhibition in HONE-1, NUGC-3, HepG2, SF-268, MCF-7, and NCI-H460 cancer cell lines, with GI₅₀ values ranging from 4 nM to 24.2 μM. 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).

• Authors: Yue-Zhi Lee, Chun-Wei Huang, Cheng-Wei Yang, Hsing-Yu Hsu, Iou-Jiun Kang, Yu-Sheng Chao, Ih-Sheng Chen, Hwan-You Chang, Shiow-Ju Lee
• Journal: Planta medica (Planta Med) Vol. 77 Issue 17 Pg. 1932-8 (Nov 2011) ISSN: 1439-0221 [Electronic] Germany
• PMID: 21728149 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Georg Thieme Verlag KG Stuttgart · New York.

Chemical References

• Alkaloids
• Anti-Inflammatory Agents
• Antineoplastic Agents, Phytogenic
• Indolizines
• Lipopolysaccharides
• Phenanthrolines
• Plant Extracts
• phenanthroindolizidine
• septicine
• Nitric Oxide
• Interferon-gamma

Topics

• Alkaloids (chemistry, isolation & purification, pharmacology)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antineoplastic Agents, Phytogenic (chemistry, pharmacology)
• Cell Line, Tumor
• Humans
• Indolizines (chemistry, isolation & purification, pharmacology)
• Interferon-gamma (pharmacology)
• Lipopolysaccharides (pharmacology)
• Medicine, Chinese Traditional
• Molecular Structure
• Nitric Oxide (metabolism)
• Phenanthrolines (chemistry, isolation & purification, pharmacology)
• Plant Extracts (chemistry, isolation & purification, pharmacology)
• Plant Leaves (chemistry)
• Plant Stems (chemistry)
• Plants, Medicinal (chemistry)
• Rats
• Structure-Activity Relationship
• Taiwan
• Tylophora (chemistry)