Mechanism of action
Miltefosine primarily acts on Leishmania by affecting the speciess promastigote and amastigote stages. Miltefosine exerts its activity by interacting with lipids, inhibiting cytochrome c oxidase and causing apoptosis-like cell death. This may affect membrane integrity and mitochondrial function of the parasite. History
Cancer
While initially studied as a cancer medication, due to side effects it was never used for this purpose.Phospholipid group alkylphosphocholine were known since the early 1980s, particularly in terms of their binding affinity with cobra venom. In 1987 the phospholipids were found to be potent toxins on leukemic cell culture. Initial in vivo investigation on the antineoplastic activity showed positive result, but then only at high dosage and at high toxicity. At the same time in Germany, Hansjörg Eibl, at the Max Planck Institute for Biophysical Chemistry, and Clemens Unger, at the University of Göttingen, demonstrated that the antineoplastic activity of the phospholipid analogue miltefosine (at the time known as hexadecylphosphocholine) was indeed tumour-specific. It was highly effective against methylnitrosourea-induced mammary carcinoma, but less so on transplantable mammary carcinomas and autochthonous benzo(a)pyrene-induced sarcomas, and relatively inactive on Walker 256 carcinosarcoma and autochthonous acetoxymethylmethylnitrosamine-induced colonic tumors of rats. It was subsequently found that miltefosine was structurally unique among lipids having anticancer property in that it lacks the glycerol group, is highly selective on cell types and acts through different mechanism.
Max Planck Innovation
FDA Panel Endorses Miltefosine for Leishmaniasis
Med India
Drugs.com