Using 5-Nitroimidazole Derivatives against Neglected Tropical Protozoan Diseases: Systematic Review

M. Vichi-Ramírez, Edgar López-López, C. Soriano-Correa, C. Barrientos-Salcedo
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Abstract

Neglected tropical diseases (NTDs) are a significant global health problem. Additionally, anti-protozoan treatments are toxic, and their therapeutic regimens require prolonged treatment times and high concentrations of the drugs. Additionally, multi-resistant protozoan strains represent an important global emergency that must be addressed. For these reasons, global efforts are being made to identify new drug candidates that are capable of combating these kinds of diseases. This systematic review shows that 5-nitroimidazole derivatives have been successfully used against neglected tropical protozoan diseases (NTPDs), with a specific focus on three diseases: malaria, leishmaniasis, and human trypanosomiasis. Some nitroimidazole derivatives have been repurposed, and an important group of new drugs is available for the treatment of NTPDs. Finally, we address 5-nitroimidazoles using chemoinformatics and medicinal chemistry tools to describe the most recent and promising 5-nitroimidazole derivatives associated with anti-protozoal activity using their published in vitro and in vivo data. We show that 5-nitroimidazoles offer a broader spectrum of activity against a variety of protozoal pathogens. More importantly, these compounds demonstrate a significantly reduced systemic toxicity compared to other nitroimidazoles. This makes them a more favorable option in the treatment of protozoal infections, particularly in scenarios where the patient’s tolerance to drug side effects is a critical concern.
使用 5-硝基咪唑衍生物防治被忽视的热带原生动物疾病:系统综述
被忽视的热带疾病(NTDs)是一个重大的全球健康问题。此外,抗原生动物治疗具有毒性,其治疗方案需要延长治疗时间和高浓度药物。此外,多重抗药性原生动物菌株也是一个必须解决的重要全球性紧急问题。因此,全球都在努力寻找能够防治这类疾病的候选新药。本系统综述显示,5-硝基咪唑衍生物已被成功用于防治被忽视的热带原生动物疾病(NTPDs),并特别关注三种疾病:疟疾、利什曼病和人类锥虫病。一些硝基咪唑衍生物已被重新利用,目前有一组重要的新药可用于治疗 NTPDs。最后,我们利用化学信息学和药物化学工具来研究 5-硝基咪唑,并利用其已发表的体外和体内数据来描述与抗原虫活性相关的最新和最有前景的 5-硝基咪唑衍生物。我们发现,5-硝基咪唑类化合物对多种原生动物病原体具有更广泛的活性谱。更重要的是,与其他硝基咪唑相比,这些化合物的全身毒性明显降低。这使它们成为治疗原生动物感染的更有利选择,尤其是在病人对药物副作用的耐受性是一个关键问题的情况下。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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