title: Screening medicinal plants for the detection of novel antimalarial products applying the inhibition of β-hematin formation.
abstract: The identification of novel scaffolds for the development of effective and safe treatments to fight malaria is urgently needed. One of the main opportunities is the discovery of new molecules from natural origin. A simple, robust and cost-effective colorimetric assay based on the inhibition of β-hematin has been adapted to routinely screen plant extracts with the ultimate goal to identify novel antimalarial ingredients. The development of this assay has included a careful optimization of all critical experimental parameters. The β-hematin assay can be completed in less than one working day, requiring a 96-well UV-vis plate reader and low-cost commercially available reagents using a standard operating protocol. It can be used on its own or in combination with the well-known Plasmodium growth inhibition assay and has the obvious merit to be informative at the early stage of drug discovery regarding the mechanism of action of the actives. A total of 40 diverse natural products and 219 plants extracts were tested. Good correlations in respect with specificity (pure compounds 85%, extracts 93%) and positive predictive value (pure compounds 72%, extracts 50%) were obtained in comparison with Plasmodium growth inhibition assay that was used as the reference assay.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Vargas
authors.forename: K
authors.initials: K
authors.lastname: Ndjoko Ioset
authors.forename: A-E
authors.initials: AE
authors.lastname: Hay
authors.forename: J-R
authors.initials: JR
authors.lastname: Ioset
authors.forename: S
authors.initials: S
authors.lastname: Wittlin
authors.forename: K
authors.initials: K
authors.lastname: Hostettmann
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000302:isolation & purification / Q000494:pharmacology*; D006420:Hemeproteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D010961:Plasmodium / Q000187:drug effects / Q000254:growth & development; D052616:Solid Phase Extraction; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000962:Antimalarials; D006420:Hemeproteins; D010936:Plant Extracts; C020753:hemozoin