title: Characterisation of Leishmania donovani promastigotes resistant to hexadecylphosphocholine (miltefosine).
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.
authors.affiliation: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
authors.forename: Karin
authors.initials: K
authors.lastname: Seifert
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Matu
authors.forename: F
authors.initials: F
authors.lastname: Javier Pérez-Victoria
authors.forename: Santiago
authors.initials: S
authors.lastname: Castanys
authors.forename: Francisco
authors.initials: F
authors.lastname: Gamarro
authors.forename: Simon L
authors.initials: SL
authors.lastname: Croft
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D016054:DNA, Protozoan / Q000235:genetics; D004351:Drug Resistance; D005784:Gene Amplification; D007893:Leishmania donovani / Q000187:drug effects* / Q000235:genetics; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000981:Antiprotozoal Agents; D016054:DNA, Protozoan; D010767:Phosphorylcholine; C039128:miltefosine