Synthesis, In Silico Study and Antimalarial Activity of Triazolo[1,5‐a]pyrimidine Derivatives

Abstract

AbstractThe present study mainly focused on synthesizing novel triazolo[1,5‐a]pyrimidine‐6‐carboxamide derivatives using multicomponent reaction. Synthesized derivatives were duly characterized using spectroscopic methods of analysis FT‐IR and mass spectroscopy, and 1H NMR and 13C NMR confirmed the structure of compounds. 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 study of all the synthesized compounds was carried out using Schrödinger LLC‐2020‐3 Software to explain the binding mode and interactions between molecules and pf DHFR enzyme. To study the drug likeliness of molecules, 3D QSAR and Pharmacokinetic studies have been carried out, and the results obtained showed a good pharmacokinetics profile of two compounds, namely AMP‐24 and AMP‐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.