Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
Department of Chemistry, Faculty of Science, University of Mohaghegh Ardabili, 56199, 11367 Ardabil, Iran.
Curr Top Med Chem. 2023;23(9):736-752. doi: 10.2174/1568026623666230201103843.
Trypanosomiasis is caused by parasitic protozoan trypanosomes in vertebrates. T. cruzi and T. brucei are causative agents of Chagas disease (CD) and Human African Trypanosomiasis (HAT), respectively. These life-threatening diseases are a serious threat to public health, with considerable incidence in sub-Saharan African and continental Latin America countries. Although WHO validated mitigated number of HAT cases in Togo (June 2020) and Cote d'Ivoire (December 2020), serious efforts need to be performed for the elimination of the disease. Antigenic variation of trypanosomal parasites provides a major bottleneck for developing effective vaccines. In the absence of human vaccines or chemoprophylaxis, the control of trypanosomatid infections may be envisaged through the eradication of vectors, management of animal reservoirs, and chemotherapy. A small number of chemical agents are currently available for antitrypanosomal treatments, and most of them are associated with toxicity, lack of efficacy, and non-oral route of administration. Given the restricted applicability of current medications, numerous efforts have been made for the synthesis and biological evaluation of heterocyclic scaffolds as antitrypanosomal candidates. In light of the above considerations, we were prompted to describe chemical diversity within privileged 5- membered heterocycles (imidazoles, thiazoles, triazoles and tetrazoles) as antitrypanosomal agents. The main purpose of the study was to throw light on the structure-activity relationship (SAR) of the relevant structures. To capture the recent structural diversity within reported cases, small molecules that belonged to the recent 7-year period (2015-2021) have been discussed. The available medications have also been briefly reviewed.
锥虫病是由脊椎动物寄生虫原生动物锥虫引起的。克氏锥虫和布氏锥虫分别是恰加斯病（CD）和人类非洲锥虫病（HAT）的病原体。这些危及生命的疾病对公共卫生构成严重威胁，在撒哈拉以南非洲和拉丁美洲大陆国家的发病率相当高。尽管世界卫生组织（WHO）证实多哥（2020 年 6 月）和科特迪瓦（2020 年 12 月）的 HAT 病例有所减少，但仍需要做出认真努力来消除这种疾病。锥虫寄生虫的抗原变异为开发有效疫苗提供了主要瓶颈。在没有人类疫苗或化学预防的情况下，可以通过消灭媒介、管理动物储存库和化疗来控制锥虫感染。目前可用于抗锥虫治疗的化学药物数量有限，其中大多数与毒性、疗效不佳和非口服给药途径有关。鉴于目前药物的应用受限，人们已经做出了许多努力，以合成和生物评价杂环支架作为抗锥虫候选物。鉴于上述考虑，我们促使描述作为抗锥虫剂的五元杂环（咪唑、噻唑、三唑和四唑）内的化学多样性。该研究的主要目的是阐明相关结构的构效关系（SAR）。为了捕捉到报告案例中最近的结构多样性，讨论了属于最近 7 年（2015-2021 年）的小分子。还简要回顾了现有的药物。
