This particular study certainly benefits the researchers interested in exploiting the antibacterial activity of thiazoles in search of novel agents.

A series of novel PABA‐substituted 1,3,5‐triazine derivatives were developed via microwave assisted synthesis and subsequently tested for antimalarial activity against chloroquine sensitive 3D7 strain of Plasmodium falciparum using chloroquine as standard. Antimalarial screening result showed that synthesized compounds exhibited IC50 in the range of 4.46 to 79.72 μg mL−1. Among the tested compounds, 4c and 4f showed significant antimalarial activity with low binding energies (BE) ‐172.32 and 160.41 kcal mol−1 via interacting with Arg122 through the involvement of COOH of the phenyl linked to 1,3,5‐triazine. In conclusion, these core scaffolds can be used for future antimalarial drug development.

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.

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The present manuscript deals with the development of novel p-aminobenzoic acid (PABA) associated 1,3,5-triazine derivatives as antimalarial agents. The molecules were developed via microwave-assisted synthesis and structures of compounds were ascertained via numerous analytical and spectroscopic techniques. The synthesized compounds were also subjected to ADMET analysis. In a docking analysis, the title compounds showed high and diverse binding affinities towards wild (−162.45 to −369.38 kcal/mol) and quadruple mutant (−165.36 to −209.47 kcal/mol) Pf-DHFR-TS via interacting with Phe58, Arg59, Ser111, Ile112, Phe116. The in vitro antimalarial activity suggested that compounds 4e, 4b, and 4h showed IC 50 ranging from 4.18 to 8.66 μg/ml against the chloroquine-sensitive (3D7) strain of Plasmodium falciparum. Moreover, compounds 4g, 4b, 4e, and 4c showed IC 50 ranging from 8.12 to 12.09 μg/ml against chloroquine-resistant (Dd2) strain. In conclusion, our study demonstrated the development of hybrid PABA substituted 1,3,5-triazines as a novel class of Pf-DHFR inhibitor for antimalarial drug discovery.