title: Antiproliferative activity of Artemisia asiatica extract and its constituents on human tumor cell lines.
abstract: The extract of Artemisia asiatica herb with antiproliferative activity against four human tumor cell lines (A2780, A431, HeLa, and MCF7) was analyzed by the MTT assay, and bioassay-directed fractionation was carried out in order to identify the compounds responsible for the cytotoxic activity. Guaianolide (1-4), seco-guianolide (5), germacranolide (6) and eudesmanolide sesquiterpenes (7), monoterpenes (8, 9), including the new compound artemisia alcohol glucoside (8), and flavonoids (10-16) were isolated as a result of a multistep chromatographic procedure (CC, CPC, PLC, and gel filtration). The compounds were identified by means of UV, MS, and NMR spectroscopy, including (1)H-and (13)C-NMR, (1)H-(1)H COSY, NOESY, HSQC, and HMBC experiments. The isolated compounds 1-16 were evaluated for their tumor cell growth-inhibitory activities on a panel of four adherent cancer cell lines, and different types of secondary metabolites were found to be responsible for the cytotoxic effects of the extract. Especially cirsilineol (13), 3β-chloro-4α,10α-dihydroxy-1α,2α-epoxy-5α,7αH-guai-11(13)-en-12,6α-olide (3), and iso-seco-tanapartholide 3-O-methyl ester (5) exerted marked cytotoxic effects against the investigated cell lines, while jaceosidin (12), 6-methoxytricin (15), artecanin (2), and 5,7,4',5'-tetrahydroxy-6,3'-dimethoxyflavone (14) were moderately active. All the sesquiterpenes and monoterpenes are reported here for the first time from this species, and in the case of artecanin (2), 3α-chloro-4β,10α-dihydroxy-1β,2β-epoxy-5α,7αH-guai-11(13)-en-12,6α-olide (4), ridentin (6), and ridentin B (7), previously unreported NMR spectroscopic data were determined.
authors.affiliation: Institute of Pharmacognosy, University of Szeged, Szeged, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Hajdú
authors.affiliation: Institute of Pharmacognosy, University of Szeged, Szeged, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Hohmann
authors.affiliation: Institute of Pharmacognosy, University of Szeged, Szeged, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Forgo
authors.affiliation: Institute of Pharmacognosy, University of Szeged, Szeged, Hungary.
authors.forename: Imre
authors.initials: I
authors.lastname: Máthé
authors.affiliation: Institute of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Molnár
authors.affiliation: Institute of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Zupkó
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D019306:Artemisia / Q000737:chemistry*; D045744:Cell Line, Tumor / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D047309:Flavones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D045788:Sesquiterpenes, Germacrane / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D047309:Flavones; D005419:Flavonoids; D010936:Plant Extracts; D012717:Sesquiterpenes; D045788:Sesquiterpenes, Germacrane; C476916:eudesmanolide; C432449:germacranolide; C477508:jaceosidin; C057618:cirsilineol