Microwave assisted synthesis, antimalarial screening and structure–activity-relationship exploration of some phenylthiazolyl-triazine derivatives against dihydrofolate reductase

In this study, a microwave-assisted methodology was first attempted to facilitate the synthesis of hybrid phenylthiazolyl-triazine derivatives. These two nuclei were clubbed together based on the structural requirement of existing antimalarial antifolates. A comparative analysis revealed that compounds synthesized using microwave-assisted procedure gave better yield and minimized the reaction time with respect to the conventional procedure. Hybrid compounds were screened for their in vitro antimalarial activity against chloroquine-sensitive (3D-7) strain of Plasmodium falciparum at 5 µg/mL and 50 µg/mL dose level. An insight into the structure–activity-relationship of the synthesized compounds was gained by docking them in the crystal structure of wild type Plasmodium falciparum dihydrofolate reductase-thymidylate synthase.