title: Effect of fluorescent dyes on in vitro-differentiated, late-stage Plasmodium falciparum gametocytes.
abstract: Plasmodium falciparum gametocytes are not associated with clinical symptoms, but they are responsible for transmitting the pathogen to mosquitoes. Therefore, gametocytocidal interventions are important for malaria control and resistance containment. Currently available drugs and vaccines are not well suited for that purpose. Several dyes have potent antimicrobial activity, but their use against gametocytes has not been investigated systematically. The gametocytocidal activity of nine synthetic dyes and four control compounds was tested against stage V gametocytes of the laboratory strain 3D7 and three clinical isolates of P. falciparum with a bioluminescence assay. Five of the fluorescent dyes had submicromolar 50% inhibitory concentration (IC50) values against mature gametocytes. Three mitochondrial dyes, MitoRed, dihexyloxacarbocyanine iodide (DiOC6), and rhodamine B, were highly active (IC(50)s < 200 nM). MitoRed showed the highest activity against gametocytes, with IC(50)s of 70 nM against 3D7 and 120 to 210 nM against clinical isolates. All compounds were more active against the laboratory strain 3D7 than against clinical isolates. In particular, the endoperoxides artesunate and dihydroartemisinin showed a 10-fold higher activity against 3D7 than against clinical isolates. In contrast to all clinically used antimalarials, several fluorescent dyes had surprisingly high in vitro activity against late-stage gametocytes. Since they also act against asexual blood stages, they shall be considered starting points for the development of new antimalarial lead compounds.
authors.affiliation: Institute of Tropical Medicine, Eberhard Karls University, Tübingen, Germany German Centre for Infection Research, Partner Site Tübingen, Tübingen, Germany Department of Medical Laboratory Sciences, College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia.
authors.forename: Tamirat
authors.initials: T
authors.lastname: Gebru
authors.affiliation: Institute of Tropical Medicine, Eberhard Karls University, Tübingen, Germany Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon German Centre for Infection Research, Partner Site Tübingen, Tübingen, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mordmüller
authors.affiliation: Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon German Centre for Infection Research, Partner Site Tübingen, Tübingen, Germany janaheld@hotmail.de.
authors.forename: Jana
authors.initials: J
authors.lastname: Held
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology; D000077332:Artesunate; D002232:Carbocyanines / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D005456:Fluorescent Dyes / Q000494:pharmacology*; D005718:Gametogenesis; D006801:Humans; D020128:Inhibitory Concentration 50; D008018:Life Cycle Stages / Q000187:drug effects*; D008163:Luminescent Measurements; D016778:Malaria, Falciparum / Q000469:parasitology; D008928:Mitochondria / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D012235:Rhodamines / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D002232:Carbocyanines; D005456:Fluorescent Dyes; D012235:Rhodamines; C007392:3,3'-dihexyl-2,2'-oxacarbocyanine; D000077332:Artesunate; C039060:artenimol; C029773:rhodamine B