title: The spiroindolone drug candidate NITD609 potently inhibits gametocytogenesis and blocks Plasmodium falciparum transmission to anopheles mosquito vector.
abstract: The global malaria agenda has undergone a reorientation from control of clinical cases to entirely eradicating malaria. For that purpose, a key objective is blocking transmission of malaria parasites from humans to mosquito vectors. The new antimalarial drug candidate NITD609 was evaluated for its transmission-reducing potential and compared to a few established antimalarials (lumefantrine, artemether, primaquine), using a suite of in vitro assays. By the use of a microscopic readout, NITD609 was found to inhibit the early and late development of Plasmodium falciparum gametocytes in vitro in a dose-dependent fashion over a range of 5 to 500 nM. In addition, using the standard membrane feeding assay, NITD609 was also found to be a very effective drug in reducing transmission to the Anopheles stephensi mosquito vector. Collectively, our data suggest a strong transmission-reducing effect of NITD609 acting against different P. falciparum transmission stages.
authors.affiliation: Medical Microbiology Department, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: van Pelt-Koops
authors.forename: H E
authors.initials: HE
authors.lastname: Pett
authors.forename: W
authors.initials: W
authors.lastname: Graumans
authors.forename: M
authors.initials: M
authors.lastname: van der Vegte-Bolmer
authors.forename: G J
authors.initials: GJ
authors.lastname: van Gemert
authors.forename: M
authors.initials: M
authors.lastname: Rottmann
authors.forename: B K S
authors.initials: BK
authors.lastname: Yeung
authors.forename: T T
authors.initials: TT
authors.lastname: Diagana
authors.forename: R W
authors.initials: RW
authors.lastname: Sauerwein
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology*; D000962:Antimalarials / Q000494:pharmacology*; D005718:Gametogenesis / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology*; D007303:Insect Vectors / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000472:pathogenicity*; D013141:Spiro Compounds / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D007211:Indoles; C552304:NITD 609; D013141:Spiro Compounds