Differential Growth Inhibitory Effects of Highly Oxygenated Guaianolides Isolated from the Middle Eastern Indigenous Plant Achillea falcata in HCT-116 Colorectal Cancer Cells

Molecules

Rita Tohme¹  Lamis Al Aaraj¹  Tarek Ghaddar¹  Hala Gali-Muhtasib¹  Najat A. Saliba¹ 

[1] AUB Nature Conservation Center, American University of Beirut, Beirut, P.O. Box 11-0236, Lebanon; E-Mails:

关键词: Achillea falcata;    sesquiterpene lactones;    guaianolides;    colorectal cancer cells;    bioassay-guided fractionation;    structure-activity relationship;   

DOI  :  10.3390/molecules18078275

来源: mdpi

【 摘 要 】

Medicinal plants play a crucial role in traditional medicine and in the maintenance of human health worldwide. Sesquiterpene lactones represent an interesting group of plant-derived compounds that are currently being tested as lead drugs in cancer clinical trials. Achillea falcata is a medicinal plant indigenous to the Middle Eastern region and belongs to the Asteraceae family, which is known to be rich in sesquiterpene lactones. We subjected Achillea falcata extracts to bioassay-guided fractionation against the growth of HCT-116 colorectal cancer cells and identified four secotanapartholides, namely 3-β-methoxy- isosecotanapartholide (1), isosecotanapartholide (2), tanaphallin (3), and 8-hydroxy-3-methoxyisosecotanapartholide (4). Three highly oxygenated guaianolides were isolated for the first time from Achillea falcata, namely rupin A (5), chrysartemin B (6), and 1β, 2β-epoxy- 3β,4α,10α-trihydroxyguaian- 6α,12-olide (7). These sesquiterpene lactones showed no or minor cytotoxicity while exhibiting promising anticancer effects against HCT-116 cells. Further structure-activity relationship studies related the bioactivity of the tested compounds to their skeleton, their lipophilicity, and to the type of functional groups neighboring the main alkylating center of the molecule.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.