Table 1.

Modes of action of current antileishmanial drugs.

Current Drugs for Leishmaniasis Treatment	Mode of Action and Parasite Targeting	References
Pentavalent Antimony (SbV)	Inhibits the mitochondrial enzyme trypanothione reductase, increasing the parasite’s susceptibility to oxidative stress generated by the macrophage during infection. It can obstruct major energy-driven pathways such as fatty acid oxidation and glycolysis.	[35,48,49]
Miltefosine (MLT)	Inhibits the enzyme cytochrome c oxidase located in the mitochondria, directly affecting energy production in the parasite. Also inhibits phosphatidylcholine synthesis, which affects lipid metabolism through the CDP-choline pathway by acting on CTP-phosphocholine cytidylyltransferase activity.	[50,51]
Liposomal amphotericin B (AmB)	Forms transmembrane channels through the cell wall and is known to have a high affinity for ergosterol, causing micropores in the membrane, increasing permeability and ion loss, and resulting in cell death.	[52,53]
Paromomycin (PMM)	Inhibits the cytosolic ribosome, affecting protein synthesis through binding to the 16S ribosomal unit and creating an alteration in its structure.	[54,55,56]
Pentamidine (PTM)	Inhibits DNA and protein synthesis and causes cell-cycle arrest in the G2/M phase. Inhibits RNA polymerase, leading to apoptosis. Inhibits arginine transport.	[57,58]