title: Differential growth inhibitory effects of highly oxygenated guaianolides isolated from the Middle Eastern indigenous plant Achillea falcata in HCT-116 colorectal cancer cells.
abstract: 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.
authors.affiliation: AUB Nature Conservation Center, American University of Beirut, Beirut, P.O. Box 11-0236, Lebanon. rgt07@aub.edu.lb
authors.forename: Rita
authors.initials: R
authors.lastname: Tohme
authors.forename: Lamis
authors.initials: L
authors.lastname: Al Aaraj
authors.forename: Tarek
authors.initials: T
authors.lastname: Ghaddar
authors.forename: Hala
authors.initials: H
authors.lastname: Gali-Muhtasib
authors.forename: Najat A
authors.initials: NA
authors.lastname: Saliba
authors.forename: Nadine
authors.initials: N
authors.lastname: Darwiche
mesh_terms: D031162:Achillea / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry; D045789:Sesquiterpenes, Guaiane / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts; D045789:Sesquiterpenes, Guaiane