Background: Presentlytheeffectiveness of antifolate antimalarial drugs is decreasing due to
the emergence of resistant Plasmodium strains. The aim of the present study was to determine the antimalarial
effect of hybrid p-bromo phenyl thiazole-triazine derivatives against 3D7 strain of Plasmodium
Methods: Seventy-fivehybrid derivativeswere designed based on the lead molecule and docking was
done against the active site of Pf-DHFR-TS (PDB i.d. 1J3i) with validated ligand fit protocol by using
Discovery Studio 2.5. Based on the highest binding energy and the best docked pose, fifteen compounds
were selected for the synthesis. Synthesized compounds were characterized by different spectroscopy
methods and in-vitro antimalarial evaluation was done against the 3D7 strain of Plasmodium falciparum.
Results: Fifteen compounds were synthesized by conventional and microwave assisted method and
were characterized byFT-IR, 1H-NMR, 13C-NMR and Mass spectroscopy. In-vitro antimalarial screening
results showed that compounds ADG303, ADG 306 and ADG 302 have the highest activity against
3D7 strain of P. falciparum. Furthermore, docking result of these compounds having binding energies
of -154.91, -165.981, -137.826 respectively showed similarity with reference compound WR99210 (-
152.023) and also bound to Asp54 and Phe 58 amino acid at the active site of the receptor.
Conclusion: The synthesized compound ADG303 exhibited an encouraging result which could be a
new lead for antimalarial drug discovery.