Bisphosphonates derived from fatty acids are potent inhibitors of Trypanosoma cruzi farnesyl pyrophosphate synthase

Bioorg Med Chem Lett. 2003 Oct 6;13(19):3231-5. doi: 10.1016/s0960-894x(03)00663-2.

Abstract

Studies on the mode of action of a series of bisphosphonates derived from fatty acids, which had previously proved to be potent inhibitors against Trypanosoma cruzi proliferation in in vitro assays, have been performed. Some of these drugs proved to be potent inhibitors against the intracellular form of the parasite, exhibiting IC(50) values at the low micromolar level. As bisphosphonates are FDA clinically approved for treatment of bone resorption disorders, their potential innocuousness makes them good candidates to control tropical diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Animals
  • Diphosphonates / chemistry
  • Diphosphonates / isolation & purification
  • Diphosphonates / pharmacology*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology*
  • Fatty Acids / chemistry
  • Fatty Acids / isolation & purification
  • Fatty Acids / pharmacology*
  • Geranyltranstransferase
  • Trypanosoma cruzi / drug effects*
  • Trypanosoma cruzi / enzymology

Substances

  • Diphosphonates
  • Enzyme Inhibitors
  • Fatty Acids
  • Alkyl and Aryl Transferases
  • Geranyltranstransferase