Design and Docking Study of Some Pyrimidine derivatives as Antimalarial Agents

Background and Aim: According to the latest estimate published by the World Health Organization in 2017, there are 219 million malaria cases and 435,000 deaths. With the emergence of drug-resistant strains in malaria, there is a need for new drug targets every time. In this study, the design and docking study of the pyrimidine derivatives for inhibiting Methionine aminopeptidase1B enzyme (Metap1b) has been considered as antimalarial agents as a new drug and against drug resistance. Methods: Docking studies were done with the AutoDock program. The structure of the molecules was drawn with the Hyperchem program and optimized by semi-empirical method. Results: Docking studies have shown that the most important links involved in drug binding are peptide receptor, π-cation and hydrogen bonding. Increasing the π-π and π-cation bonds in enhancing the strength of this group of compounds is effective. It was also found that Combination No. 7 was the most effective compound in binding to the active site of the enzyme. Conclusion: Based on the results of docking studies, all designed compounds exhibit significant inhibitory effects on the active site of the enzyme, but the compound 7 showed the best inhibitory effect. According to the results of cheminformatics, compound 7 can be a candidate for a new anti-malarial drug.