Postgraduate Program in Pharmaceutical Sciences, State University of Paraíba, Campina Grande, 58429-500, Brazil; Cesmac University Center, Pharmacy Departament, Maceió, Brazil; Drug Development and Synthesis Laboratory, Department of Pharmacy, State University of Paraíba, Campina Grande, 58429-500, Brazil.
Postgraduate Program in Pharmaceutical Sciences, State University of Paraíba, Campina Grande, 58429-500, Brazil; Drug Development and Synthesis Laboratory, Department of Pharmacy, State University of Paraíba, Campina Grande, 58429-500, Brazil.
Eur J Med Chem. 2023 Oct 5;258:115550. doi: 10.1016/j.ejmech.2023.115550. Epub 2023 Jun 8.
Neglected tropical diseases (NTDs) constitute a group of approximately 20 infectious diseases that mainly affect the impoverished population without basic sanitation in tropical countries. These diseases are responsible for many deaths worldwide, costing billions of dollars in public health investment to treat and control these infections. Among them are the diseases caused by protozoa of the Trypanosomatid family, which constitute Trypanosoma cruzi (Chagas disease), Trypanosoma brucei (sleeping sickness), and Leishmaniasis. In addition, there is a classification of other diseases, called the big three, AIDS, tuberculosis, and malaria, which are endemic in countries with tropical conditions. Despite the high mortality rates, there is still a gap in the treatment. The drugs have a high incidence of side effects and protozoan resistance, justifying the investment in developing new alternatives. In fact, the Target-Based Drug Design (TBDD) approach is responsible for identifying several promising compounds, and among the targets explored through this approach, N-myristoyltransferase (NMT) stands out. It is an enzyme related to the co-translational myristoylation of N-terminal glycine in various peptides. The myristoylation process is a co-translation that occurs after removing the initiator methionine. This process regulates the assembly of protein complexes and stability, which justifies its potential as a drug target. In order to propose NMT as a potential target for parasitic diseases, this review will address the entire structure and function of this enzyme and the primary studies demonstrating its promising potential against Leishmaniasis, T. cruzi, T. brucei, and malaria. We hope our information can help researchers worldwide search for potential drugs against these diseases that have been threatening the health of the world's population.
被忽视的热带病（NTDs）是一组约 20 种传染病，主要影响热带国家缺乏基本卫生条件的贫困人口。这些疾病在全球范围内造成了许多死亡，为了治疗和控制这些感染，公共卫生投资了数十亿美元。其中包括由原生动物门锥体虫科引起的疾病，包括克氏锥虫（恰加斯病）、布氏锥虫（昏睡病）和利什曼病。此外，还有其他一些疾病的分类，称为三大疾病，即艾滋病、结核病和疟疾，这些疾病在热带条件的国家中流行。尽管死亡率很高，但治疗仍存在差距。这些药物副作用发生率高，原生动物耐药性强，因此有必要投资开发新的替代品。事实上，基于靶点的药物设计（TBDD）方法负责鉴定出几种有前途的化合物，而在这种方法中探索的靶点中，N-豆蔻酰转移酶（NMT）引人注目。它是一种与各种肽中 N 端甘氨酸的共翻译豆蔻酰化有关的酶。豆蔻酰化过程是在去除起始甲硫氨酸后发生的共翻译过程。该过程调节蛋白复合物的组装和稳定性，这证明了它作为药物靶点的潜力。为了将 NMT 作为寄生虫病的潜在靶点，本综述将讨论该酶的整个结构和功能，以及证明其对利什曼病、克氏锥虫、布氏锥虫和疟疾有潜在应用前景的初步研究。我们希望我们的信息能帮助全世界的研究人员寻找针对这些威胁世界人口健康的疾病的潜在药物。
