title: Antiprotozoal Activity-Based Profiling of a Dichloromethane Extract from Anthemis nobilis Flowers.
abstract: A dichlomethane extract of Anthemis nobilis flower cones showed promising in vitro antiprotozoal activity against Trypanosoma brucei rhodesiense and Leishmania donovani, with IC50values of 1.43 ± 0.50 and 1.40 ± 0.07 μg/mL, respectively. A comprehensive profiling of the most active fractions afforded 19 sesquiterpene lactones, including 15 germacranolides, two seco-sesquiterpenes, one guaianolide sesquiterpene lactone, and one cadinane acid. Of these, 13 compounds were found to be new natural products. The compounds were characterized by extensive spectroscopic data analysis (1D and 2D NMR, HRMS, circular dichroism) and computational methods, and their in vitro antiprotozoal activity was evaluated. The furanoheliangolide derivative 15 showed high potency and selectivity in vitro against T. b. rhodesiense bloodstream forms (IC500.08 ± 0.01 μM; SI 63). In silico calculations were consistent with the drug-like properties of 15.
authors.affiliation: Department of Pharmaceutical Biology, University of Basel , Klingelbergstrasse 50, 4056 Basel, Switzerland.
authors.forename: Maria
authors.identifier: 0000-0001-5567-2072
authors.initials: M
authors.lastname: De Mieri
authors.affiliation: Department of Pharmaceutical Biology, University of Basel , Klingelbergstrasse 50, 4056 Basel, Switzerland.
authors.forename: Giannicola
authors.initials: G
authors.lastname: Monteleone
authors.affiliation: Department of Pharmaceutical Biology, University of Basel , Klingelbergstrasse 50, 4056 Basel, Switzerland.
authors.forename: Isidor
authors.initials: I
authors.lastname: Ismajili
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute , Socinstrasse 57, 4000 Basel, Switzerland.|University of Basel , Petersplatz 1, 4001 Basel, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.affiliation: Department of Pharmaceutical Biology, University of Basel , Klingelbergstrasse 50, 4056 Basel, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hamburger
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D031167:Chamaemelum; D035264:Flowers / Q000737:chemistry*; D005663:Furans / Q000494:pharmacology; D007783:Lactones / Q000737:chemistry; D007893:Leishmania donovani / Q000187:drug effects; D008752:Methylene Chloride; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D045788:Sesquiterpenes, Germacrane / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D054830:Sesterterpenes; D014344:Trypanocidal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects; D014349:Trypanosoma cruzi / Q000187:drug effects
chemical_list: D000981:Antiprotozoal Agents; D001952:Bridged-Ring Compounds; D005663:Furans; D007783:Lactones; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; D045788:Sesquiterpenes, Germacrane; D054830:Sesterterpenes; D014344:Trypanocidal Agents; C508039:cadinane; C499803:furanoheliangolide; C432449:germacranolide; D008752:Methylene Chloride