Synthesis and Evaluation of Methyl 4-(7-Hydroxy-4,4,8-Trimethyl-3-Oxabicyclo[3.3.1]Nonan-2-yl)Benzoate as an Antileishmanial Agent and Its Synergistic Effect with Miltefosine

Antimicrob Agents Chemother. 2018 Jan 25;62(2):e01810-17. doi: 10.1128/AAC.01810-17. Print 2018 Feb.

Abstract

In our interest in oxabicyclic compounds as potent antileishmanial agents, the present work deals with the chemical synthesis of a new oxabicyclic derivative, methyl 4-(7-hydroxy-4,4,8-trimethyl-3-oxabicyclo[3.3.1]nonan-2-yl)benzoate (PS-207). This oxabicyclic derivative showed a good antileishmanial effect on the parasite, on both the promastigote and the amastigote. The mode of parasitic death from PS-207 seemed to be apoptosis-like. Interestingly, the combination of PS-207 with a low dose of miltefosine showed a synergistic effect against the parasite.

Keywords: Leishmania donovani; drug development; miltefosine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiprotozoal Agents / pharmacology*
  • Apoptosis / drug effects
  • Benzoates / pharmacology*
  • Cell Line, Tumor
  • Humans
  • Inhibitory Concentration 50
  • Leishmania donovani / drug effects*
  • Leishmaniasis, Visceral / drug therapy*
  • Leishmaniasis, Visceral / microbiology
  • Phosphorylcholine / analogs & derivatives*
  • Phosphorylcholine / pharmacology
  • U937 Cells

Substances

  • Antiprotozoal Agents
  • Benzoates
  • Phosphorylcholine
  • miltefosine