Chagas disease affects around 8 million people worldwide and its treatment depends on only two nitroheterocyclic drugs, benznidazole (BZD) and nifurtimox (NFX). Both drugs have limited curative power in chronic phase of disease. Nifuroxazide (NF), a nitroheterocyclic drug, was used as lead to design a set of twenty one compounds in order to improve the anti-Trypanosoma cruzi activity. Lipinski's rules were considered in order to support drug-likeness designing. The set of N′-[(5-nitrofuran-2-yl) methylene] substituted hydrazides was assayed against three T. cruzi strains, which represent the discrete typing units more prevalent in human patients: Y (TcII), Silvio X10 cl1 (TcI), and Bug 2149 cl10 (TcV). All the derivatives, except one, showed enhanced trypanocidal activity against the three strains as compared to BZD. In the Y strain 62% of the compounds were more active than NFX. The most active compound was N′-((5-nitrofuran-2-yl) methylene)biphenyl-4-carbohydrazide (C20), which showed IC₅₀ values of 1.17 ± 0.12 μM; 3.17 ± 0.32 μM; and 1.81 ± 0.18 μM for Y, Silvio X10 cl1, and Bug 2149 cl10 strains, respectively. Cytotoxicity assays with human fibroblast cells have demonstrated high selectivity indices for several compounds. Exploratory data analysis indicated that primarily topological, steric/geometric, and electronic properties have contributed to the discrimination of the set of investigated compounds. The findings can be helpful to drive the designing, and subsequently, the synthesis of additional promising drugs against Chagas disease.

查加斯病影响全球约800万人，其治疗仅取决于两种硝基杂环药物，即苯硝唑（BZD）和硝呋替莫斯（NFX）。两种药物在疾病的慢性期均具有有限的疗效。为了提高抗克氏锥虫的活性，使用了一种硝基杂环药物Nifuroxazide（NF）来设计21种化合物。考虑了Lipinski的规则以支持类似药物的设计。针对三个克鲁氏梭菌测定了一组N '-[（5-硝基呋喃-2-基亚甲基）亚甲基]取代的酰肼代表人类患者中更常见的离散分型单位的菌株：Y（TcII），Silvio X10 cl1（TcI）和Bug 2149 cl10（TcV）。与BZD相比，除一种衍生物外，所有衍生物均对三种菌株表现出增强的锥虫杀灭活性。在Y菌株中，有62％的化合物比NFX更具活性。最具活性的化合物是N '-（（（5-硝基呋喃-2-基）亚甲基）联苯-4-碳酰肼（C20），显示IC ₅₀值为1.17±0.12μM; 3.17±0.32μM; 对于Y，Silvio X10 cl1和Bug 2149 cl10菌株分别为1.81±0.18μM。用人成纤维细胞进行细胞毒性试验已证明了对几种化合物的高选择性指数。探索性数据分析表明，主要是拓扑，空间/几何和电子特性已导致对所研究化合物的区分。这些发现有助于推动设计，以及随后合成其他有前景的抗南美锥虫病药物的研究。