Orabi Mohamed A A, Alshahrani Mohammed Merae, Sayed Ahmed M, Abouelela Mohamed E, Shaaban Khaled A, Abdel-Sattar El-Shaymaa
Department of Pharmacognosy, College of Pharmacy, Najran University, Najran 61441, Saudi Arabia.
Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Najran University, Najran 61441, Saudi Arabia.
Metabolites. 2023 Jan 6;13(1):93. doi: 10.3390/metabo13010093.
Leishmaniasis is a group of infectious diseases caused by protozoa. The ineffectiveness, high toxicity, and/or parasite resistance of the currently available antileishmanial drugs has created an urgent need for safe and effective leishmaniasis treatment. Currently, the molecular-docking technique is used to predict the proper conformations of small-molecule ligands and the strength of the contact between a protein and a ligand, and the majority of research for the development of new drugs is centered on this type of prediction. N-myristoyltransferase (NMT) has been shown to be a reliable therapeutic target for investigating new anti-leishmanial molecules through this kind of virtual screening. Natural products provide an incredible source of affordable chemical scaffolds that serve in the development of effective drugs. leaves, roots, and fruits have been shown to contain withanolide and other phytomolecules that are efficient anti-protozoal agents against , and spp. Through a review of previously reported compounds from -afforded 35 alkaloid, phenolic, and steroid compounds and 132 withanolides/derivatives, typical of the genus. These compounds were subjected to molecular docking screening and molecular dynamics against NMT. Calycopteretin-3-rutinoside and withanoside IX showed the highest affinity and binding stability to NMT, implying that these compounds could be used as antileishmanial drugs and/or as a scaffold for the design of related parasite NMT inhibitors with markedly enhanced binding affinity.
利什曼病是由原生动物引起的一组传染病。目前可用的抗利什曼病药物的无效性、高毒性和/或寄生虫耐药性，使得迫切需要安全有效的利什曼病治疗方法。目前，分子对接技术用于预测小分子配体的正确构象以及蛋白质与配体之间的接触强度，大多数新药研发研究都集中在这类预测上。N-肉豆蔻酰基转移酶（NMT）已被证明是通过这种虚拟筛选来研究新型抗利什曼病分子的可靠治疗靶点。天然产物提供了令人难以置信的、价格合理的化学支架来源，可用于开发有效药物。已证明叶、根和果实含有睡茄内酯和其他植物分子，这些是针对利什曼原虫属、硕大利什曼原虫和热带利什曼原虫的有效抗原虫剂。通过对先前报道的来自蒺藜科的化合物进行综述，得到了35种生物碱、酚类和甾体化合物以及132种睡茄内酯/衍生物，这是蒺藜属的典型化合物。对这些化合物进行了针对NMT的分子对接筛选和分子动力学研究。三叶豆紫檀苷和睡茄苷IX对NMT表现出最高的亲和力和结合稳定性，这意味着这些化合物可用作抗利什曼病药物和/或用作设计具有显著增强结合亲和力的相关寄生虫NMT抑制剂的支架。
