Synthesis, in silico study and antimalarial activity of 2-thioxo-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-5-carboxamide derivatives

The present study mainly focused on synthesizing novel 2-thioxo-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-5-carboxamide derivatives using multicomponent reaction. Further, the potential of the synthesized compounds against Plasmodium falciparum dihydrofolate reductase (Pf-DHFR) inhibitors was evaluated by in vitro antimalarial activity, and the results of the study showed moderate to good antimalarial profile of synthesized entities. In-silico research of all the synthesized compounds was conducted using Schr & ouml;dinger LLC-2020-3 software to explain the binding mode and interactions between molecules and the Pf-DHFR enzyme. To study the drug likeliness of molecules, 3D QSAR and pharmacokinetic studies have been carried out, and the results obtained showed good pharmacokinetics profile of two compounds, namely AMPS-26 and AMPS-28, having good IC50 values concerning standard drugs. Further, the in vitro enzyme inhibition assay results suggested that the synthesized compound interacts nicely with the enzyme and might be used as a potent antimalarial agent.Graphical abstractThe current study presents a synthesis of the novel 2-thioxo-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-5-carboxamide derivatives using multicomponent reaction. A series of 30 compounds is synthesized. Amongst them, AMPS-28 (IC50 value 0.028 mu g/mL) is found to be the most potent against Pf-DHFR enzyme, which is based on its molecular docking studies and IC50 values, comparable to pyrimethamine having IC50 value 0.035 mu g/mL.