Ministry of Fisheries and Livestock, Department of Veterinary Services, Mulungushi House, P.O. Box 50600, Ridgeway, Lusaka 15100, Zambia.
Unit for Environmental Science and Management, Faculty of Natural and Agricultural Sciences, North-West University, Potchefstroom 2531, South Africa.
Molecules. 2021 Jun 2;26(11):3372. doi: 10.3390/molecules26113372.
African trypanosomes cause diseases in humans and livestock. Human African trypanosomiasis is caused by and . Animal trypanosomoses have major effects on livestock production and the economy in developing countries, with disease management depending mainly on chemotherapy. Moreover, only few drugs are available and these have adverse effects on patients, are costly, show poor accessibility, and parasites develop drug resistance to them. Therefore, novel trypanocidal drugs are urgently needed. Here, the effects of synthesized nitrofurantoin analogs were evaluated against six species/strains of animal and human trypanosomes, and the treatment efficacy of the selected compounds was assessed in vivo. Analogs and , containing 11- and 12-carbon aliphatic chains, respectively, showed the highest trypanocidal activity (IC < 0.34 µM) and the lowest cytotoxicity (IC > 246.02 µM) in vitro. Structure-activity relationship analysis suggested that the trypanocidal activity and cytotoxicity were related to the number of carbons in the aliphatic chain and electronegativity. In vivo experiments, involving oral treatment with nitrofurantoin, showed partial efficacy, whereas the selected analogs showed no treatment efficacy. These results indicate that nitrofurantoin analogs with high hydrophilicity are required for in vivo assessment to determine if they are promising leads for developing trypanocidal drugs.
非洲锥体虫会导致人类和家畜患病。人类非洲锥虫病是由 和 引起的。动物锥虫病对发展中国家的畜牧业生产和经济有重大影响，其疾病管理主要依赖化疗。此外，可用的药物很少，这些药物对患者有不良反应，成本高，可及性差，寄生虫对它们产生耐药性。因此，迫切需要新型杀锥虫药物。在这里，评估了合成的硝基呋喃妥因类似物对六种动物和人类锥体虫的作用，并用体内实验评估了所选化合物的治疗效果。含有 11 个和 12 个碳原子的脂肪链的类似物 和 表现出最高的杀锥虫活性（IC < 0.34 µM）和最低的细胞毒性（IC > 246.02 µM）。构效关系分析表明，杀锥虫活性和细胞毒性与脂肪链中的碳原子数和电负性有关。体内实验涉及用硝基呋喃妥因进行口服治疗，显示出部分疗效，而所选类似物则没有治疗效果。这些结果表明，需要具有高亲水性的硝基呋喃妥因类似物进行体内评估，以确定它们是否是开发杀锥虫药物的有前途的先导化合物。
