Characterisation of Leishmania donovani promastigotes resistant to hexadecylphosphocholine (miltefosine) |
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| Authors: | Seifert Karin Matu Sangeeta Javier Pérez-Victoria F Castanys Santiago Gamarro Francisco Croft Simon L |
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| Affiliation: | Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. |
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| 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. |
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