The spiroindolone drug candidate NITD609 potently inhibits gametocytogenesis and blocks Plasmodium falciparum transmission to anopheles mosquito vector

Antimicrob Agents Chemother. 2012 Jul;56(7):3544-8. doi: 10.1128/AAC.06377-11. Epub 2012 Apr 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anopheles / parasitology*
  • Antimalarials / pharmacology*
  • Gametogenesis / drug effects*
  • Indoles / pharmacology*
  • Insect Vectors / parasitology*
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / pathogenicity*
  • Spiro Compounds / pharmacology*

Substances

  • Antimalarials
  • Indoles
  • NITD 609
  • Spiro Compounds