o-(chloroacetylcarbamoyl)fumagillol and miltefosine

We investigate the role of methionine aminopeptidase 2 (MAP2) in miltefosine induced programmed cell death (PCD) in promastigote form of L. donovani. We report that TNP-470, an inhibitor of MAP2, inhibits programmed cell death in miltefosine treated promastigotes. It inhibits the biochemical features of metazoan apoptosis, including caspase3/7 protease like activity, oligonucleosomal DNA fragmentation, collapse of mitochondrial transmembrane potential, and increase in cytosolic pool of calcium ions but did not prevent the cell death and phosphatidyl serine externalization. The data suggests that the MAP2 is involved in the regulation of PCD in parasite. Moreover, TNP-470 shows the leishmanicidal activity (IC

Topics: Aminopeptidases; Antiprotozoal Agents; Cell Death; Cloning, Molecular; Cyclohexanes; DNA Fragmentation; Gene Expression Regulation; Leishmania donovani; Metalloendopeptidases; O-(Chloroacetylcarbamoyl)fumagillol; Phosphorylcholine; Protozoan Proteins; Sesquiterpenes