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Acanthamoeba is a free-living amoeba that is an opportunistic pathogen of humans and animals.  Its prognosis is potentially poor that requires fast diagnosis and successful treatment. There are two phases in its life cycle: an active trophozoite form and the double-walled resistant cyst. This amoebic genus is the causative agent of two severe diseases in humans: Acanthamoeba keratitis (AK) and fatal granulomatous amoebic encephalitis (GAE). Acanthamoeba cysts almost remain viable after treatments and lead to serious and frequent recurrence of infection. Resistance of the double walled cysts is mainly due to cellulose molecules presented in the inner layer of the cysts. Thus, cellulose degradation or inhibiting the cellulose synthesis offers a potential strategy for effective treatment of Acanthamoeba. In this non-systematic review we aimed at providing an overview of the cellulose structure, its role in skeletal structure and also physicochemical activity of the protozoa and present it as new drug target for the treatment of amoebic infection. Overall, the degradation of the cyst wall will make amoeba susceptible to chemotherapeutic drugs, and at least inhibition of Acanthamoeba excystment, consequently it prevents the recurrence of infection. Furthermore, cellulose synthesis inhibitors cause current drugs to affect on Acanthamoeba in lower time and concentrations. Therefore, using compounds or drugs that inhibit the synthesis of cellulose can be a new treatment for amoebic infections.

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Leishmaniasis is a major public health problem, but so far there are no effective commercially available vaccines for this disease. Its control strategy is only reliant on therapy, but currently the drugs available for the treatment of leishmaniasis are also limited and a great concern is the rapid rate of resistance to common drugs. The first step in discovery and development of new drugs is to identify an appropriate drug target. Accordingly, it is important to recognize the metabolic pathways in which the leishmania parasites live and selecting a target in the parasite biological pathway, absent in the host or different from the host homolog. Discovery of new drugs requires high costs and takes a lot of time (up to 15 years). Therefore, choosing the approved drugs in the market for various diseases, including leishmaniasis is very cost-effective considering the mechanism of drug action and other aspects. Miltefosin is an effective anti-cancer agent that is also used for different types of leishmaniasis. In recent years, researchers have focused on the anti-leishmanial effects of pharmaceutical compounds or anticancer drugs to find more effective compounds with lower side effects. The present article mainly reviews the anticancer drugs that have been tested for their anti-leishmanial effects in both in vitro and in vivo conditions.
 
 

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Leishmaniasis is a vector-borne zoonotic disease caused by various species of the genus Leishmania, (trypanosomatidae family) that is transmitted by phlebotomine sandflies. The disease can present in a range of clinical forms, including dermal lesions, metastasis mucocutaneous forms, and fatal visceral forms. In this non-systematic review, we aimed at introducing the role of kinetoplast DNA (kDNA) and dependent topoisomerases (TPI) as potential chemotherapeutic targets for treatment of leishmaniasis. The Leishmania parasite has a mitochondrial DNA located in the attached circles. KDNA replication process is very complex and a large number of proteins are involved. Some of them are classified as topoisomerases, which play major biological roles in the effective cell processes in the topology, synthesis, and organization of kDNA and constitute the main drug target in kinetoplast for leishmaniasis cure. Several studies have shown that the inhibitors of TPI exchange these enzymes into intracellular cell toxins and provide an appropriate tool for killing the parasite in the host. DNA binding drugs have also been reported as therapeutic agents against leishmanial infections.
 

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 Background and purpose: Leishmaniasis is one of the most important infectious diseases caused by different species of the Leishmania, which is a public health problem worldwide. So far, no effective vaccine is introduced for this disease and drug therapy is associated with many side effects. Therefore, this study was designed to identify novel FDA-approved compounds with anti-leishmanial activity.
Materials and methods: In this experimental study, proteomics, protein network analysis, and molecular docking were used. Protein profile was identified by LC-MS/MS and protein network analysis was performed using Cytoscape. Processing of the compound structure and molecular docking was performed by HyperChem and AutoDock Vina, respectively. Finally, docking results were interpreted by LigPlot⁺.
Results: Based on proteomics and protein network analysis, glycosomal malate dehydrogenase was suggested as a potential drug target. Among the compounds, the best docking results were associated with Conivaptan and Avodart with a binding energy level of -10.5 and -10.2, respectively. Also, molecular docking studies showed that the most important bonds involved in drug-receptor binding were hydrogen and hydrophobic bonds.
Conclusion: The current study demonstrated the importance of integrated proteomics, protein network and docking to identify novel compounds with anti-Leishmania properties. According to this study, Conivaptan and Avodart, also approved by the Food and Drug Administration, are effective inhibitors of glycosomal malate dehydrogenase in Leishmania major and Leishmania tropica which meanwhile require further in-vitro and in-vivo experiments.