title: 9β-hydroxyparthenolide esters from Inula montbretiana and their antiprotozoal activity.
abstract: In continuation of ongoing studies on the potential of natural products as antiprotozoal leads or drugs, it was found that the CH₂Cl₂ extract obtained from the flowering aerial parts of Inula montbretiana DC. (Asteraceae, tribe Inuleae) displays antiprotozoal activity, especially against Trypanosoma brucei rhodesiense (IC₅₀: 3.38 µg/mL). Isolation of the possible active constituents led to the identification of six sesquiterpene lactones, all esters of 9 β-hydroxyparthenolide. Two isolates, namely, 9 β-(3',4'-epoxy-3'-methylpentanoyloxy)-parthenolide and 9 β-(3'-oxo-2'-methylbutanoyloxy)-parthenolide, represented diastereomeric mixtures differing only in the configuration within the acyl moieties. According to in vitro test results, the mixture of esters with diastereomeric 3,4-epoxy-3-methylpentanoic acid was the most active constituent against Trypanosoma brucei rhodesiense (IC₅₀: 0.26 µg/mL) and was less cytotoxic against rat skeletal myoblasts (L6 cell line) with a selectivity index of about 9. The mixture of diastereomeric 2-methyl-3-oxobutyric acid esters was the most potent against Plasmodium falciparum (IC₅₀: 1.48 µg/mL) and displayed a selectivity index of about 35.
authors: Ankara University, Faculty of Pharmacy, Department of Pharmacognosy, Ankara, Turkey.
authors: Alper
authors: A
authors: Gökbulut
authors: Marcel
authors: M
authors: Kaiser
authors: Reto
authors: R
authors: Brun
authors: Engin
authors: E
authors: Sarer
authors: Thomas J
authors: TJ
authors: Schmidt
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D004952:Esters / Q000302:isolation & purification / Q000494:pharmacology; D035264:Flowers / Q000737:chemistry; D038143:Inula / Q000737:chemistry*; D007893:Leishmania donovani / Q000187:drug effects; D023421:Models, Animal; D008517:Phytotherapy; D035261:Plant Components, Aerial / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects; D051381:Rats; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects; D014349:Trypanosoma cruzi / Q000187:drug effects; D014421:Turkey
chemical_list: D000981:Antiprotozoal Agents; D004952:Esters; D010936:Plant Extracts; D012717:Sesquiterpenes; C002669:parthenolide