Identification of Agents with Potential Leishmania Malate Dehydrogenase Inhibitor Activity: A Proteomic and Molecular Docking Approach

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.

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+.

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.

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.