Programa de pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Feira de Santana, Feira de Santana, Brazil.
Programa de pós-graduação em Biotecnologia, Universidade Estadual de Feira de Santana, Feira de Santana, Brazil.
J Biomol Struct Dyn. 2021 Jun;39(9):3378-3386. doi: 10.1080/07391102.2020.1763837. Epub 2020 May 13.
Malaria is an infectious disease caused by protozoa of the genus spp. with approximately 219 million cases in 2017. is main responsible for the most severe form of the disease, cerebral malaria. Despite of public health impacts, chemotherapy against malaria is still limited due to the emergence of drug resistance cases used in monotherapy and combination therapies. Thus, the development of new antimalarial drugs becomes emergency. One way of achieve this goal is to explore essential and/or unique therapeutic targets of the parasite, or at least sufficiently different to ensure selective inhibition. Enoil-ACP reductase (ENR) is a NADH-dependent enzyme responsible for the limiting step of the type II fatty acid biosynthetic pathway (FAS II). Thus, pharmacophore and docking based virtual screening were applied to prioritize molecules for assays against W2 strain. The application of successive filters at OOCC database (=618) resulted in the identification of one molecule (13) (EC = 0.098±0.021μM) with similar biological activity to artemether. The molecule 13 is a typical drug repurposing case due to previous other approved therapeutic uses on Chinese medicine as a non-specific cholinergic antagonist, thus it could be accelerated the drug development process. Additionally, molecular dynamics studies were used to confirm stability of the molecular interactions identified by molecular docking. Thus, representative structures of ENR can be used in a study to propose new derivatives for evaluation of biological activity and . Communicated by Ramaswamy H. Sarma.
疟疾是一种由 spp. 属原生动物引起的传染病，2017 年有大约 2.19 亿例病例。 是导致最严重形式疟疾（脑型疟疾）的主要原因。尽管对公共卫生有影响，但由于单药和联合疗法中耐药病例的出现，抗疟疾化疗仍然受到限制。因此，开发新的抗疟药物成为当务之急。实现这一目标的一种方法是探索寄生虫的必需和/或独特的治疗靶点，或者至少足够不同以确保选择性抑制。烯醇-ACP 还原酶（ENR）是一种 NADH 依赖性酶，负责 II 型脂肪酸生物合成途径（FAS II）的限速步骤。因此，基于药效团和对接的虚拟筛选被应用于针对 W2 株的 进行 测定的优先化分子。在 OOCC 数据库（=618）中应用连续过滤器导致鉴定出一种与青蒿素具有相似生物活性的分子（13）（EC=0.098±0.021μM）。分子 13 是一个典型的药物再利用案例，因为它之前在中国医学中被批准用于非特异性胆碱能拮抗剂的其他治疗用途，因此可以加速药物开发过程。此外，分子动力学研究用于确认分子对接鉴定的分子相互作用的稳定性。因此，可以使用 ENR 的代表性结构来研究提出新的衍生物以评估生物活性 和 。由 Ramaswamy H. Sarma 传达。
