Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, India.
School of Pharmacy, Graphic Era Hill University, Dehradun, Uttarakhand, India.
J Biochem Mol Toxicol. 2021 Mar;35(3):e22682. doi: 10.1002/jbt.22682. Epub 2020 Dec 17.
Malaria continues to become a major global health problem, particularly in Sub-Saharan Africa, Asia, and Latin America. The widespread emergence of resistance to first-line drugs has further bolstered an urgent need for a new and cost-effective antimalarial(s). Thus, the present study enumerates the synthesis of novel hybrid dimethoxy pyrazole 1,3,5-triazine derivatives 7(a-j) and their in silico results short-listed three compounds with good binding energies and dock scores. Docking analysis shows that hydrogen-bonding predominates and typically involves key residues, such as Asp54, Tyr170, Ile164, and Arg122. The in vitro antimalarial evaluation of three top-ranked compounds (7e, 7g, and 7h) showed half-maximal inhibitory concentration values range from 53.85 to 100 μg/ml against chloroquine-sensitive strain 3D7 of Plasmodium falciparum. Compound 7e may be utilized as a lead for further optimization work in drug discovery due to good antimalarial activity.
疟疾仍然是一个主要的全球健康问题，特别是在撒哈拉以南非洲、亚洲和拉丁美洲。对一线药物的广泛耐药性的出现进一步加剧了对新的、具有成本效益的抗疟药物的迫切需求。因此，本研究列举了新型杂合二甲氧基吡唑 1,3,5-三嗪衍生物 7(a-j)的合成及其入选的三个具有良好结合能和对接分数的化合物的计算结果。对接分析表明氢键占主导地位，通常涉及关键残基，如 Asp54、Tyr170、Ile164 和 Arg122。三种排名靠前的化合物（7e、7g 和 7h）的体外抗疟评估表明，对氯喹敏感的恶性疟原虫 3D7 株的半数最大抑制浓度值范围为 53.85 至 100μg/ml。由于具有良好的抗疟活性，化合物 7e 可作为进一步优化药物发现的先导化合物。
