{"title":"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","authors":"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","doi":"10.1016/j.arcmed.2024.102958","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p><span><span>Chagas disease and </span>cutaneous leishmaniasis, two parasitic diseases caused by </span><span><em>Trypanosoma cruzi</em></span> (<em>T. cruzi</em>) and <span><em>Leishmania mexicana</em></span> (<em>L. mexicana</em><span>), 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.</span></p></div><div><h3>Methods</h3><p><span><span>Using molecular docking, this work describes a structure-based virtual screening of an FDA-approved </span>drug library against </span><em>Trypanosoma cruzi</em> and <em>Leishmania mexicana</em><span><span> glycolytic enzyme </span>triosephosphate isomerase<span> (TIM), which is highly conserved in these parasites. The selected compounds with potential dual inhibitory activity were tested </span></span><em>in vitro</em> to confirm their biological activity.</p></div><div><h3>Results</h3><p><span>The study showed that five compounds: nilotinib<span><span>, chlorhexidine, </span>protriptyline<span>, cyproheptadine, and montelukast, were more active against </span></span></span><em>T. cruzi</em><span><span>, than the reference drugs, nifurtimox and </span>benznidazole while chlorhexidine and protriptyline were the most active against </span><em>L. mexicana</em>.</p></div><div><h3>Conclusions</h3><p>The analysis of these compounds and their structural characteristics may provide the basis for the development of new antiprotozoal agents.</p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":4.7000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Repositioning FDA-Approved Drug Against Chagas Disease and Cutaneous Leishmaniosis by Structure-Based Virtual Screening\",\"authors\":\"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\",\"doi\":\"10.1016/j.arcmed.2024.102958\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p><span><span>Chagas disease and </span>cutaneous leishmaniasis, two parasitic diseases caused by </span><span><em>Trypanosoma cruzi</em></span> (<em>T. cruzi</em>) and <span><em>Leishmania mexicana</em></span> (<em>L. mexicana</em><span>), 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.</span></p></div><div><h3>Methods</h3><p><span><span>Using molecular docking, this work describes a structure-based virtual screening of an FDA-approved </span>drug library against </span><em>Trypanosoma cruzi</em> and <em>Leishmania mexicana</em><span><span> glycolytic enzyme </span>triosephosphate isomerase<span> (TIM), which is highly conserved in these parasites. The selected compounds with potential dual inhibitory activity were tested </span></span><em>in vitro</em> to confirm their biological activity.</p></div><div><h3>Results</h3><p><span>The study showed that five compounds: nilotinib<span><span>, chlorhexidine, </span>protriptyline<span>, cyproheptadine, and montelukast, were more active against </span></span></span><em>T. cruzi</em><span><span>, than the reference drugs, nifurtimox and </span>benznidazole while chlorhexidine and protriptyline were the most active against </span><em>L. mexicana</em>.</p></div><div><h3>Conclusions</h3><p>The analysis of these compounds and their structural characteristics may provide the basis for the development of new antiprotozoal agents.</p></div>\",\"PeriodicalId\":8318,\"journal\":{\"name\":\"Archives of Medical Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2024-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of Medical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0188440924000110\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Medical Research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0188440924000110","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
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.
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.