Open Access
Review
Table 1
Classical monotherapies used for Leishmania infection.
| Compound | Commercial name | Average cost in US$ [4, 14, 57] | Route of administration | Mechanism of action | References |
|---|---|---|---|---|---|
| Sodium stibogluconate (SSG) | Pentostam® | Cost of VL treatment in Sudan: 450 | IM/IV | Unclear, but can lead to inhibition of DNA topoisomerase I and increased ROS production. To date it remains unknown if it is the pentavalent form or the reduced trivalent form exerting leishmanicidal activity. | [28] |
| Meglumine antimoniate | Glucantime® | Cost of VL treatment in Brazil IM: 418.52/IV 669.40 Cost of mucosal leishmaniasis treatment in Brazil 167.66 | IM/IV/IL | Unclear, but induces DNA damage mediated by oxidative stress and glutathione (GSH) depletion. | [61] |
| Amphotericin B deoxycholate | Fungizone® | Cost of VL treatment in Brazil 1522.70 | IV | Interaction with membrane ergosterol, pore formation, and leakage of cytosolic content. Sequestration of cholesterol abrogating parasite/macrophage interaction. Functional gene overexpression leading to ROS and Ca2+ increase, cytochrome-c liberation and metacaspase activation, inducing DNA fragmentation and apoptosis. Immunomodulation of chemokines and cytokines, including IL-1B, leading to increasing NO levels. | [12] |
| Liposomal Amphotericin B | AmBisome® | Cost of VL treatment in Brazil 659.79 to 11,559.15Cost of mucosal leishmaniasis treatment in Brazil: 715.35In South-East Asia and East Africa: Donation of the drug for VL treatment from Gilead Science | IV | ||
| Miltefosine | Impavido® | Cost of mucosal leishmaniasis treatment in Brazil: 259.92 | O | Inhibition of phosphatidylcholine and sphingomyelin biosynthesis leading to apoptosis. Disruption of Ca2+ homeostasis, alkalinization of acidocalcisomes. Induction of IFN-g, leading to a Th1 inflammatory profile. Respiratory chain disruption by cytochrome-c inhibition. | [12] |
| Paromomycin | Humatin® | IM | Affects Leishmania cytosolic RNA translation and intracellular trafficking by inhibition of protein synthesis and targeting the decoding center of ribosomes. | [16, 86] | |
| Pentamidine | Pentacarinat® | IM/IV | Unclear, but other diamine compounds exert their activity by accumulating and blocking the replication of Leishmania kinetoplast DNA. | [113] |
IM: intramuscular; IV: intravenous; IL: intralesional, O: oral.
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