Acta Tropica 81 (2002) 151–157 Sensitivities of Leishmania species to hexadecylphosphocholine (miltefosine), ET-18-OCH 3 (edelfosine) and amphotericin B Patricia Escobar, Sangeeta Matu, Cla ´udia Marques, Simon L. Croft * Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK Received 2 July 2001; received in revised form 1 October 2001; accepted 23 October 2001 Abstract The sensitivities of both promastigote and amastigote stages of six species of Leishmania, L. donoani, L. major, L. tropica, L. aethiopica, L. mexicana and L. panamensis, were determined in vitro to the phospholipid drugs hexadecylphosphocholine (HPC, miltefosine) and ET-18-OCH 3 (edelfosine). In all assays L. donoani was the most sensitive species, with ED 50 values in the range of 0.12–1.32 M against promastigotes and 1.2 – 4.6 M against amastigotes. L. major was the least sensitive species in the majority of assays with ED 50 values for HPC in the range of 4.8–13.1 M against promastigotes and for HPC and ET-18-OCH 3 in the range of 7.5–37.1 M against amastigotes. Amphotericin B deoxycholate was used as the standard drug and gave submicromolar ED 50 values in all assays; L. mexicana was the least sensitive species to this drug. © 2002 Elsevier Science B.V. All rights reserved. Keywords: Alkyl-lysophospholipids; Hexadecylphosphocholine; ET-18-OCH 3 ; Amphotericin B; Leishmania species www.parasitology-online.com 1. Introduction The current situation for the chemotherapy of leishmaniasis is more promising than it has been for several decades with both new drugs and new formulations of old drugs in clinical trial (Berman, 1997; Croft and Karbwang, 2000). Re- cently hexadecylphosphocholine (HPC, miltefos- ine), an alkylphosphocholine originally developed as an anti-cancer drug (Brachwitz and Vollgraf, 1995), has proved to be an effective treatment for visceral leishmaniasis (VL) in India, including an- timony resistant cases, (Sundar et al., 1998; Jha et al., 1999) and has been hailed as potentially the first oral treatment for this disease (Herwaldt, 1999). Miltefosine has also been reported as an effective oral treatment for human cutaneous leishmaniasis cases in Colombia (Soto et al., 2001). These clinical trials followed experimental studies that demonstrated alkylphosphocholines, including HPC, and alkylglycerophosphocholines, including other anti-cancer agents ET-18-OCH 3 (edelfosine), BM 41.440 (ilmofosine) and SRI- 62,834, to be active in vitro against L. donoani * Corresponding author. Tel.: +44-20-7927-2345; fax: + 44-20-7323-5687. E-mail address: simon.croft@lshtm.ac.uk (S.L. Croft). 0001-706X/02/$ - see front matter © 2002 Elsevier Science B.V. All rights reserved. PII:S0001-706X(01)00197-8