Novel Agents against Miltefosine-Unresponsive Leishmania donovani

Antimicrob Agents Chemother. 2015 Dec;59(12):7826-9. doi: 10.1128/AAC.00928-15. Epub 2015 Sep 21.

Abstract

Visceral leishmaniasis is a deadly endemic disease. Unresponsiveness to the only available oral drug miltefosine poses a big challenge for the chemotherapy of the disease. We report a novel molecule, PS-203 {4-(4,4,8-trimethyl-7-oxo-3-oxabicyclo[3.3.1]non-2-yl)-benzoic acid methyl ester}, as effective against a miltefosine-unresponsive strain of the parasite. Further, combinations of PS-203 with miltefosine were also evaluated and showed promising results against a miltefosine-unresponsive strain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiprotozoal Agents / chemical synthesis
  • Antiprotozoal Agents / pharmacology*
  • Benzoates / chemical synthesis
  • Benzoates / pharmacology*
  • Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Resistance / drug effects*
  • Drug Synergism
  • Humans
  • Leishmania donovani / drug effects*
  • Leishmania donovani / growth & development
  • Macrophages / drug effects
  • Macrophages / parasitology
  • Parasitic Sensitivity Tests
  • Phosphorylcholine / analogs & derivatives
  • Phosphorylcholine / pharmacology

Substances

  • 4-(4,4,8-trimethyl-7-oxo-3-oxabicyclo(3.3.1)non-2-yl)benzoic acid methyl ester
  • Antiprotozoal Agents
  • Benzoates
  • Bridged Bicyclo Compounds, Heterocyclic
  • Phosphorylcholine
  • miltefosine