Docking, synthesis and Antimalarial Evaluation of Hybrid Phenyl Thiazole 1,3,5-Triazine Derivatives

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Author(s): Arpita Das*, Surajit K. Ghosh, Hans Raj Bhat, Junmoni Kalita, Ankita Kashyap, Nayana Adhikari.

Journal Name: Current Bioactive Compounds

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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 falciparum.

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.

Keywords: Antimalarial , Molecular Docking , Triazine , Para bromo phenyl thiazole

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(E-pub Ahead of Print)
DOI: 10.2174/1573407215666190308154139
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