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The Amphotericin B–miltefosine–sterol complex is a specialized molecular assembly that occurs within the plasma membranes of protozoan parasites, notably Leishmania species, during synergistic drug treatment. This complex is formed when the polyene antibiotic Amphotericin B binds to ergosterol, the fungal and protozoal equivalent of cholesterol, to create transmembrane pores [1, 2]. The inclusion of Miltefosine, an alkylphosphocholine, into the membrane environment alters the lipid architecture and fluidity, which enhances the formation and stability of these Amphotericin B-induced pores [3, 4]. This tripartite interaction leads to a catastrophic loss of membrane selective permeability, resulting in the leakage of essential ions like potassium and the eventual death of the parasite [1]. From a clinical perspective, the formation of these complexes is the basis for combination therapies that aim to increase efficacy while minimizing the toxic side effects of the individual drugs [5]. Understanding the structural dynamics of this complex is crucial for overcoming drug resistance in neglected tropical diseases [3].
The complex facilitates the formation of transmembrane pores and disrupts lipid bilayer organization, leading to the leakage of essential ions and subsequent parasite cell death [1, 2, 4].
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