Plasmodium falciparum parasites overexpressing farnesyl diphosphate synthase/geranylgeranyl diphosphate synthase are more resistant to risedronate

Mem Inst Oswaldo Cruz. 2018;113(10):e180174. doi: 10.1590/0074-02760180174. Epub 2018 Aug 13.

Abstract

Farnesyl diphosphate synthase/geranylgeranyl diphosphate synthase (FPPS/GGPPS) is a key enzyme in the synthesis of isoprenic chains. Risedronate, a bisphosphonate containing nitrogen (N-BP), is a potent inhibitor of blood stage Plasmodium. Here, we show that P. falciparum parasites overexpressing FPPS/GGPPS are more resistant to risedronate, suggesting that this enzyme is an important target, and bisphosphonate analogues can be used as potential antimalarial drugs.

MeSH terms

  • Analysis of Variance
  • Animals
  • Antimalarials / analysis
  • Antimalarials / pharmacology*
  • Blotting, Western
  • Drug Resistance
  • Farnesyltranstransferase / analysis
  • Farnesyltranstransferase / biosynthesis*
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / enzymology*
  • Plasmodium falciparum / growth & development
  • Reference Values
  • Risedronic Acid / analysis
  • Risedronic Acid / pharmacology*

Substances

  • Antimalarials
  • Farnesyltranstransferase
  • Risedronic Acid