METHODS: In this study, ten compounds 7(a-j) were synthesized by using nucleophilic substitution reaction, screened for in silico study and their antimalarial activity were evaluated against 3D7 (chloroquine-sensitive) strain of P. falciparum.
RESULTS: The present work involves the development of hybrid trimethoxy pyrazole 1,3,5-triazine derivatives 7 (a-j). Through in silico analysis, four compounds were identified with favorable binding energy and dock scores. The primary focus of the docking investigations was on the examination of hydrogen bonding and the associated interactions with certain amino acid residues, including Arg A122, Ser A108, Ser A111, Ile A164, Asp A54, and Cys A15. The IC50 values of the four compounds were measured in vitro to assess their antimalarial activity against the chloroquine sensitive 3D7 strain of P. falciparum. The IC50 values varied from 25.02 to 54.82 μg/mL.
CONCLUSIONS: Among the ten derivatives, compound 7J has considerable potential as an antimalarial agent, making it a viable contender for further refinement in the realm of pharmaceutical exploration, with the aim of mitigating the global malaria load.
方法:在本研究中,利用亲核取代反应合成了10个化合物7(a-j),筛选用于计算机模拟研究,并针对恶性疟原虫的3D7(氯喹敏感)菌株评估了其抗疟活性。
结果:本工作涉及杂化三甲氧基吡唑1,3,5-三嗪衍生物7(a-j)的开发。通过硅分析,鉴定出四种化合物具有良好的结合能和对接得分。对接研究的主要重点是检查氢键和与某些氨基酸残基的相关相互作用,包括ArgA122,SerA108,SerA111,IleA164,AspA54和CysA15。在体外测量四种化合物的IC50值以评估它们对恶性疟原虫的氯喹敏感性3D7菌株的抗疟活性。IC50值在25.02至54.82μg/mL之间变化。
结论:在十种衍生物中,化合物7J作为抗疟药具有相当大的潜力,使其成为药物探索领域进一步完善的可行竞争者,以减轻全球疟疾负荷。