title: Chemical constituents from Waltheria indica exert in vitro activity against Trypanosoma brucei and T. cruzi.
abstract: Six extracts from the roots and the aerial parts of Waltheria indica L. (Malvaceae) were screened for their in vitro antitrypanosomal activity towards Trypanosoma brucei brucei STIB 427 strain, T. brucei rhodesiense STIB 900 and Trypanosoma cruzi Tulahuen C4. The dichloromethane extract from the roots showed the highest activity against T. cruzi (IC50=0.74 μg/mL) as well as a good selectivity index (SI value of 35). Based on these results, this extract was fractionated and led to the isolation of three alkaloids (adouetin X (1), waltheriones A (2) and C (3)) and three pentacyclic triterpene derivatives (betulinic acid (4), 3β-acetoxy-27-trans-caffeoyloxyolean-12-en-28-oic acid methyl ester (5) and 3β-acetoxy-27-cis-caffeoyloxyolean-12-en-28-oic acid methyl ester (6)) identified by 1D and 2D NMR, UV, IR and MS analyses. Among these, waltherione C exhibited the highest and selective antitrypanosomal activity towards T. cruzi (IC50=1.93 μM) with low cytotoxicity (IC50=101.23 μM), resulting in a selectivity index value of 52. Waltherione C conforms to hit activity criteria with respect to T. cruzi as required by the WHO/TDR.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland.
authors.forename: Sylvian
authors.initials: S
authors.lastname: Cretton
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland.
authors.forename: Lise
authors.initials: L
authors.lastname: Bréant
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland.
authors.forename: Lucie
authors.initials: L
authors.lastname: Pourrez
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ambuehl
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland.
authors.forename: Remo
authors.initials: R
authors.lastname: Perozzo
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland.
authors.forename: Laurence
authors.initials: L
authors.lastname: Marcourt
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstr. 57, 4051 Basel, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland.
authors.forename: Muriel
authors.initials: M
authors.lastname: Cuendet
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland. Electronic address: philippe.christen@unige.ch.
authors.forename: Philippe
authors.initials: P
authors.lastname: Christen
mesh_terms: D042462:4-Quinolones / Q000737:chemistry / Q000302:isolation & purification; D000470:Alkaloids / Q000737:chemistry* / Q000302:isolation & purification; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000302:isolation & purification; D002460:Cell Line; D020128:Inhibitory Concentration 50; D019660:Malvaceae / Q000737:chemistry*; D015394:Molecular Structure; D035261:Plant Components, Aerial / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D051381:Rats; D014315:Triterpenes / Q000737:chemistry* / Q000302:isolation & purification; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D042462:4-Quinolones; D000470:Alkaloids; D000981:Antiprotozoal Agents; D010936:Plant Extracts; D014315:Triterpenes; C587675:waltherione C
keywords: Alkaloids; Antitrypanosomal activity; Chagas disease; Pentacyclic triterpenes; Waltheria indica