Abstract

Chagas disease kills over 10,000 people per year, and approximately 8 million people are infected by Trypanosoma cruzi. The reference drug for treatment of the disease, benznidazole, is the same since the 70s. In recent years, many CYP51 inhibitors were tested against this parasite’s target. One of them, posaconazole, was even tested in clinical trials that unfortunately were not successful. Nevertheless, there are still many evidences that CYP51 is a great potential target to treat T. cruzi infection. The research for new effective molecules that can cure the chronic phase of the disease is essential. 2D and 3D-quantitative structure activity relationship (QSAR) studies were conducted in this work to create three QSAR models using the chemical structures of 197 published compounds that already went through either in vivo or in vitro tests. After the analysis of the models, new analogues not yet synthesized were suggested here and had their biological activity and synthetic availability assessed.

Graphic abstract

中文翻译：

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使用 QSAR 研究规划新的克氏锥虫 CYP51 抑制剂。

摘要

南美锥虫病每年导致 10,000 多人死亡，大约 800 万人感染了克氏锥虫。治疗该病的参考药物苯硝唑，自70年代以来一直相同。近年来，针对这种寄生虫的靶点测试了许多 CYP51 抑制剂。其中之一，泊沙康唑，甚至在临床试验中进行了测试，但不幸的是没有成功。尽管如此，仍有许多证据表明 CYP51 是治疗T. cruzi的巨大潜在靶点感染。研究可以治愈疾病慢性期的新有效分子至关重要。在这项工作中进行了 2D 和 3D 定量结构活性关系 (QSAR) 研究，以使用已通过体内或体外测试的 197 种已发表化合物的化学结构创建三个 QSAR 模型。在对模型进行分析之后，这里提出了尚未合成的新类似物，并评估了它们的生物活性和合成可用性。

图形摘要