在这项研究中,我们使用了计算机技术来确定可用的寄生虫治疗方法,代表着一个有希望的治疗途径。基于我们的计算计划,旨在发现来自寄生虫的各种靶酶的天然抑制剂,从而导致被忽视的热带病(NTDs),我们提出了关于三种姜黄衍生的植物化学物质作为利什曼原虫蝶啶还原酶I(PTR1)抑制剂的新发现。PTR1是锥虫寄生虫独特叶酸代谢的关键酶,具有既定的治疗意义。采用教育部软件,分子对接分析评估姜黄植物化学物质对抗利什曼原虫PTR1的功效。通过RMSD值为2来确认对接协议的验证。对接后,选择与关键残基显着相互作用的化合物以及在-6和-8kcal/mol之间的结合亲和力进行相互作用模式探索。测试十二种姜黄植物化学物质,包括姜黄素,ingiberene,curcumol,姜黄烯醇,丁香酚,双去甲氧基姜黄素,四氢姜黄素,三乙基姜黄素,姜黄酮,Turmerin,去甲氧基姜黄素,和turmeronols,显示结合亲和力范围为-5.5至-8kcal/mol。值得注意的是,姜黄素,去甲氧基姜黄素,和双去甲氧基姜黄素表现出-6.5至-8kcal/mol的结合亲和力,并与催化残基建立了实质性的相互作用。这些植物化学物质有望成为针对利什曼原虫的合理药物设计的先导结构。PTR在未来的应用中。这项工作强调了这些已确定的植物化学物质在开发更有效的抑制剂方面的潜力,证明了它们在解决由寄生虫引起的被忽视的热带病方面的相关性。
In this study, we used in silico techniques to identify available parasite treatments, representing a promising therapeutic avenue. Building upon our computational initiatives aimed at discovering natural inhibitors for various target enzymes from parasites causing neglected tropical diseases (NTDs), we present novel findings on three turmeric-derived phytochemicals as inhibitors of Leishmania pteridine reductase I (PTR1) through in silico methodologies. PTR1, a crucial enzyme in the unique folate metabolism of trypanosomatid parasites, holds established therapeutic significance. Employing MOE software, a molecular docking analysis assesses the efficacy of turmeric phytochemicals against Leishmania PTR1. Validation of the docking protocol is confirmed with an RMSD value of 2. Post-docking, compounds displaying notable interactions with critical residues and binding affinities ranging between -6 and -8 kcal/mol are selected for interaction pattern exploration. Testing twelve turmeric phytochemicals, including curcumin, zingiberene, curcumol, curcumenol, eugenol, bisdemethoxycurcumin, tetrahydrocurcumin, tryethylcurcumin, turmerones, turmerin, demethoxycurcumin, and turmeronols, revealed binding affinities ranging from -5.5 to -8 kcal/mol. Notably, curcumin, demethoxycurcumin, and bisdemethoxycurcumin exhibit binding affinities within -6.5 to -8 kcal/mol and establish substantial interactions with catalytic residues. These phytochemicals hold promise as lead structures for rational drug design targeting Leishmania spp. PTR in future applications. This work underscores the potential of these identified phytochemicals in the development of more effective inhibitors, demonstrating their relevance in addressing neglected tropical diseases caused by parasites.