J Brindha, M Balamurali M, Chanda Kaushik
Division of Chemistry, School of Advanced Sciences, Vellore Institute of Technology, Chennai, India.
Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology, Vellore, India.
Front Chem. 2021 Mar 12;9:622286. doi: 10.3389/fchem.2021.622286. eCollection 2021.
Neglected tropical diseases (NTDs) as termed by WHO include twenty different infectious diseases that are caused by bacteria, viruses, and parasites. Among these NTDs, Chagas disease and leishmaniasis are reported to cause high mortality in humans and are further associated with the limitations of existing drugs like severe toxicity and drug resistance. The above hitches have rendered researchers to focus on developing alternatives and novel therapeutics for the treatment of these diseases. In the past decade, several target-based drugs have emerged, which focus on specific biochemical pathways of the causative parasites. For leishmaniasis, the targets such as nucleoside analogs, inhibitors targeting nucleoside phosphate kinases of the parasite's purine salvage pathway, 20S proteasome of , mitochondria, and the associated proteins are reviewed along with the chemical structures of potential drug candidates. Similarly, in case of therapeutics for Chagas disease, several target-based drug candidates targeting sterol biosynthetic pathway (C14-ademethylase), L-cysteine protease, heme peroxidation, mitochondria, farnesyl pyrophosphate, etc., which are vital and unique to the causative parasite are discussed. Moreover, the use of nano-based formulations towards the therapeutics of the above diseases is also discussed.
世界卫生组织(WHO)所称的被忽视热带病(NTDs)包括由细菌、病毒和寄生虫引起的20种不同的传染病。在这些被忽视热带病中,恰加斯病和利什曼病据报道会导致人类高死亡率,并且还与现有药物的局限性相关,如严重毒性和耐药性。上述问题使得研究人员专注于开发治疗这些疾病的替代药物和新型疗法。在过去十年中,出现了几种基于靶点的药物,它们专注于致病寄生虫的特定生化途径。对于利什曼病,本文综述了核苷类似物、针对寄生虫嘌呤补救途径的核苷磷酸激酶的抑制剂、线粒体的20S蛋白酶体以及相关蛋白质等靶点,以及潜在候选药物的化学结构。同样,对于恰加斯病的治疗,本文讨论了几种针对甾醇生物合成途径(C14-脱甲基酶)、L-半胱氨酸蛋白酶、血红素过氧化、线粒体、法尼基焦磷酸等靶点的基于靶点的候选药物,这些靶点对于致病寄生虫至关重要且具有独特性。此外,本文还讨论了纳米制剂在上述疾病治疗中的应用。