Antiproliferative and apoptotic sesquiterpene lactones from Carpesium faberi

• Published in: Bioorganic & medicinal chemistry letters 2011-01, Vol.21 (1), p.366-372
• Main Authors: Li, Xu-Wen, Weng, Liang, Gao, Xue, Zhao, Yun, Pang, Fei, Liu, Jian-Hui, Zhang, Hong-Feng, Hu, Jin-Feng
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - toxicity; Antiproliferative; Apoptosis; Asteraceae - chemistry; Biological and medical sciences; breast neoplasms; Carpesium; Carpesium faberi; cell cycle; Cell Line, Tumor; Compositae; diterpenoids; flow cytometry; General pharmacology; Humans; inhibitory concentration 50; Lactones - chemistry; Lactones - isolation & purification; Lactones - toxicity; Magnetic Resonance Spectroscopy; Medical sciences; Molecular Conformation; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Plant Extracts - chemistry; Sesquiterpene lactones; Sesquiterpenes - chemistry; sesquiterpenoid lactones; spectroscopy
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.10.138

Four new (1–4) and 13 known sesquiterpene lactones together with two known diterpenes were isolated from Carpesium faberi. All isolated compounds were evaluated for their antiproliferative activities against MCF-7 human breast cancer cells using the MTT assay. The sesquiterpene lactones (except tomentosin 17) possessing an α-methylene-γ-lactone moiety were found to have significant antiproliferative activities. The cell cycle-specific inhibition and apoptosis induced by selected compounds were investigated using flow cytometry (FCM). Four new (1–4) and 13 known (5–17) sesquiterpene lactones along with two known diterpenes (18, 19) were isolated from the whole plant of Carpesium faberi. The new structures were elucidated by means of spectroscopic techniques and some chemical transformations to be pseudoguaian-1α(H)-8α,12-olide-4β-O-β-d-glucopyranoside (1), 4β,10α-dihydroxy-5α(H)-1,11(13)-guaidien-8α,12-olide (2), 4β,10β-dihydroxy-5α(H)-1, 11(13)-guaidien-8β,12-olide (3), and (4S)-acetyloxyl-11(13)-carabren-8β,12-olide (4). All isolates were tested against MCF-7 human breast cancer cells using the MTT assay. Among them, the sesquiterpene lactones (except tomentosin 17) possessing an α-methylene-γ-lactone moiety were found to have in vitro antiproliferative activities, with IC50 values of 3.0–38.8μg/mL. The effects of four selected sesquiterpene lactones (guaianolide 2, carabranolide 4, pseudoguaianolide 9, eudesmanolide 13) on the cell cycle were examined using flow cytometry (FCM).