title: An unusual dimeric guaianolide with antiprotozoal activity and further sesquiterpene lactones from Eupatoriumperfoliatum.
abstract: The CH(2)Cl(2) extract of aerial parts of Eupatorium perfoliatum L. exhibits antiprotozoal activity under in vitro conditions, especially against Plasmodium falciparum (IC(50)=2.7μg/ml). The search for active compounds yielded seven sesquiterpene lactones: Four structurally similar guaianolides, one dimeric guaianolide, and two germacranolides. The guaianolides differ in the degree of oxidation at C-14, ranging from a hydroxyl group up to a free carboxylic acid. The dimeric guaianolide, structurally closely related to the monomers, displays an unusual type of interguaianolide linkage between C-14 and C-4. Except for the germacranolide euperfolitin, all STLs described here were hitherto unknown. Furthermore, the flavonoid aglycones eupafolin, hispidulin, patuletin, and kaempferol were identified in the extract, which, except for kaempferol, have not been described as constituents of E. perfoliatum before. The dimeric guaianolide was shown to be the most active constituent against Plasmodium falciparum (IC(50) = 2.0μM) and was less cytotoxic against rat skeletal myoblasts (IC(50) = 16.2μM, selectivity index of about 8).
authors.affiliation: Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Hittorfstraße 56, D-48149 Münster, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: Maas
authors.forename: Andreas
authors.initials: A
authors.lastname: Hensel
authors.forename: Fernando Batista da
authors.initials: FB
authors.lastname: Costa
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D019281:Dimerization; D036602:Eupatorium / Q000737:chemistry*; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D007783:Lactones / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D008752:Methylene Chloride / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D032446:Myoblasts / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects; D051381:Rats; D045789:Sesquiterpenes, Guaiane / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000981:Antiprotozoal Agents; D005419:Flavonoids; D007783:Lactones; D045789:Sesquiterpenes, Guaiane; D008752:Methylene Chloride