Characterisation of Leishmania Donovani Promastigotes Resistant to Hexadecylphosphocholine (Miltefosine)

Int J Antimicrob Agents. 2003 Oct;22(4):380-7. doi: 10.1016/s0924-8579(03)00125-0.

Abstract

Leishmania donovani promastigote lines resistant to hexadecylphosphocholine (HePC, miltefosine) at 2.5, 5.0, 10.0, 20.0 and 40.0 microM were developed in vitro by continuous step-wise drug pressure. The 40 microM line was 15 times more resistant to HePC than the wild-type clone and showed cross-resistance to the ether lipid ET-18-OCH3 (edelfosine) but not to the standard anti-leishmanial drugs. Resistance was stable up to 12 weeks in drug-free culture medium. No amplification of specific genes, including the multidrug resistance P-glycoprotein gene, could be detected in the resistant parasites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Animals
  • Antiprotozoal Agents / pharmacology*
  • DNA, Protozoan / genetics
  • Drug Resistance
  • Gene Amplification
  • Leishmania donovani / drug effects*
  • Leishmania donovani / genetics
  • Phosphorylcholine / analogs & derivatives*
  • Phosphorylcholine / pharmacology*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antiprotozoal Agents
  • DNA, Protozoan
  • Phosphorylcholine
  • miltefosine