通过基于结构的虚拟筛选重新定位 FDA 批准的抗击南美锥虫病和皮肤利什曼病的药物

IF 4.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Alfredo Juarez-Saldivar , Rogelio Gómez-Escobedo , Gerardo Corral-Ruiz , Karla Fabiola Chacón-Vargas , Vanessa Horta-Montaño , Luvia Sanchez-Torres , Lenci k. Vazquez-Jimenez , Benjamín Nogueda-Torres , Gildardo Rivera
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引用次数: 0

摘要

背景恰加斯病和皮肤利什曼病是分别由克鲁斯锥虫(T. cruzi)和墨西哥利什曼原虫(L. mexicana)引起的两种寄生虫病,对全球具有重大影响。本研究利用分子对接技术,对美国食品药物管理局批准的针对克鲁兹锥虫和墨西哥利什曼原虫糖酵解酶三糖磷酸异构酶(TIM)的药物库进行了基于结构的虚拟筛选。研究结果表明,尼洛替尼、氯雷他定、普罗替林、环丙吡啶和孟鲁司特这五种化合物对克鲁兹锥虫的活性高于参考药物氯雷他定、普罗替林、环丙吡啶和孟鲁司特。结论对这些化合物及其结构特征的分析可为开发新的抗原虫药物提供依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Repositioning FDA-Approved Drug Against Chagas Disease and Cutaneous Leishmaniosis by Structure-Based Virtual Screening

Background

Chagas disease and cutaneous leishmaniasis, two parasitic diseases caused by Trypanosoma cruzi (T. cruzi) and Leishmania mexicana (L. mexicana), respectively, have a major global impact. Current pharmacological treatments for these diseases are limited and can cause severe side effects; thus, there is a need for new antiprotozoal drugs.

Methods

Using molecular docking, this work describes a structure-based virtual screening of an FDA-approved drug library against Trypanosoma cruzi and Leishmania mexicana glycolytic enzyme triosephosphate isomerase (TIM), which is highly conserved in these parasites. The selected compounds with potential dual inhibitory activity were tested in vitro to confirm their biological activity.

Results

The study showed that five compounds: nilotinib, chlorhexidine, protriptyline, cyproheptadine, and montelukast, were more active against T. cruzi, than the reference drugs, nifurtimox and benznidazole while chlorhexidine and protriptyline were the most active against L. mexicana.

Conclusions

The analysis of these compounds and their structural characteristics may provide the basis for the development of new antiprotozoal agents.

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来源期刊
Archives of Medical Research
Archives of Medical Research 医学-医学:研究与实验
CiteScore
12.50
自引率
0.00%
发文量
84
审稿时长
28 days
期刊介绍: Archives of Medical Research serves as a platform for publishing original peer-reviewed medical research, aiming to bridge gaps created by medical specialization. The journal covers three main categories - biomedical, clinical, and epidemiological contributions, along with review articles and preliminary communications. With an international scope, it presents the study of diseases from diverse perspectives, offering the medical community original investigations ranging from molecular biology to clinical epidemiology in a single publication.
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