Synthesis of 16-mercaptohexadecylphosphocholine, a miltefosine analog with leishmanicidal activity.
The alkylphosphocholine miltefosine (n-hexadecylphosphocholine, MT) has been introduced recently as a very effective drug for the oral treatment of human leishmaniasis. However, the parasiticidal mechanism of MT at a molecular level is far from being understood. Here we report the synthesis and biological characterization of 16-mercaptohexadecylphosphocholine, a thiol analog of MT which was designed to facilitate the search of MT interacting targets within the parasite by a variety of analytical methods. This analog presents the same leishmanicidal effect as the parent drug against Leishmania donovani promastigotes and Leishmania pifanoi axenic amastigotes, and has been used to develop an affinity chromatography method to attempt the isolation of putative Leishmania proteins that bind to the phosphocholine part of the molecule.
Hornillos
Valentín
V
Instituto de Química Orgánica, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
Saugar
José María
JM
de la Torre
Beatriz G
BG
Andreu
David
D
Rivas
Luis
L
Acuña
A Ulises
AU
Amat-Guerri
Francisco
F
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002846:Chromatography, Affinity / Q000379:methods; D006801:Humans; D007891:Leishmania / Q000187:drug effects*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015800:Protozoan Proteins / Q000302:isolation & purification; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology
D000981:Antiprotozoal Agents; D015800:Protozoan Proteins; D013438:Sulfhydryl Compounds; D010767:Phosphorylcholine; C039128:miltefosine