Identification and Introduction of Possible Inhibitors of Plasmodium Falciparum Lactate Dehydrogenase Enzyme using Computational Techniques of Drug Design and Virtual Screening based on Macromolecules

Abstract

Introduction: Human malaria is an infectious-blood disease that is caused by the Plasmodium genus. Anopheles mosquitoes transmit malaria by biting and are well-known as the only biological carriers of this disease. The aim of this research was the identification and introduction of possible inhibitors of Plasmodium falciparum lactate dehydrogenase enzyme using computational techniques of drug design and virtual screening based on macromolecule. Methods: In this analytical-descriptive study, 8733 compounds were initially collected from the PubChem database. In the second step, different filtrations were performed on the library compounds. The selected compounds showed good drug-like properties and pharmacokinetics. Finally, molecular docking simulations were carried out to investigate their binding mode and interactions in the enzyme's active site. Results: The results of the present study showed that the bonds involved in the binding of the compounds with the enzyme were hydrophobic interactions and hydrogen bonds, and the π-π interaction was in the lower priority. Among the studied compounds, the best docking results were related to the compounds with identification codes CID_23603310, CID_23603337, CID_11912187 and CID_11912184 and free binding energy of -29.10, -9.06, -9.04 and -9.00 kcal/mol, respectively. In general, lipophilic parts and hydrogen bonds increased the affinity and inhibited the enzyme. Conclusion: Based on the results, all the compounds showed suitable connections in the active site of the enzyme and can be proposed as potential effective inhibitors of Plasmodium falciparum lactate dehydrogenase enzyme.

Keywords

• molecular docking
• drug-likeness
• pharmacokinetics
• malaria.