Alfredo Juarez-Saldivar, Lenci K Vazquez-Jimenez, Eyra Ortíz-Pérez, Rogelio Gomez-Escobedo, Benjamin Nogueda-Torres, Gildardo Rivera
{"title":"Virtual Screening of FDA-Approved Drugs on Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) to Obtain New Trypanocidal Agents.","authors":"Alfredo Juarez-Saldivar, Lenci K Vazquez-Jimenez, Eyra Ortíz-Pérez, Rogelio Gomez-Escobedo, Benjamin Nogueda-Torres, Gildardo Rivera","doi":"10.2174/0115734064408199251003102853","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>The protozoan parasite Trypanosoma cruzi (T. cruzi) is the etiologic agent of Chagas disease, also known as American trypanosomiasis, which primarily affects the Americas and is highly prevalent in developing countries. Treatment consists of the drugs nifurtimox and benznidazole; however, both drugs have variable efficacy and cause serious adverse effects. In T. cruzi, the enzyme glyceraldehyde 3-phosphate dehydrogenase (TcGAPDH) plays an essential role in energy production and additional nuclear functions, making it a pharmacological target for the development of new trypanocidal agents. In this study, the objective was to identify new potential TcGAPDH inhibitors with trypanocidal activity.</p><p><strong>Methods: </strong>A virtual screening based on molecular docking of FDA-approved drugs was performed, followed by in vitro biological evaluation of trypomastigotes from two T. cruzi strains.</p><p><strong>Results: </strong>Seven FDA-approved drugs (pemetrexed, gliquidone, irbesartan, enoxacin, norfloxacin, pazopanib, and fenoprofen) had the best affinity values and a suitable interaction profile at the active site of the TcGAPDH enzyme, which had better LC50 values than the reference drugs.</p><p><strong>Discussion: </strong>Drug repositioning using computer-aided methods reduces cost and time to find new pharmacological treatments. In this study, gliquidone (antidiabetic), irbesartan (antihypertensive), pemetrexed, and pazopanib (anticancer) are drugs with high trypanocidal activity that could be candidates for evaluation in clinical phases or used to develop new drugs to combat Chagas disease. It highlights fenoprofen, an anti-inflammatory agent, which has biological properties that help to reduce the symptomatology of the disease in the chronic stage. Additionally, it is necessary to study the mechanism of action of these compounds in detail to confirm if they have an effect on the proposed pharmacological targets.</p><p><strong>Conclusion: </strong>Seven FDA-approved drugs are candidates for further studies leading to the development of potential new treatments for Chagas disease.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":2.5000,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115734064408199251003102853","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: The protozoan parasite Trypanosoma cruzi (T. cruzi) is the etiologic agent of Chagas disease, also known as American trypanosomiasis, which primarily affects the Americas and is highly prevalent in developing countries. Treatment consists of the drugs nifurtimox and benznidazole; however, both drugs have variable efficacy and cause serious adverse effects. In T. cruzi, the enzyme glyceraldehyde 3-phosphate dehydrogenase (TcGAPDH) plays an essential role in energy production and additional nuclear functions, making it a pharmacological target for the development of new trypanocidal agents. In this study, the objective was to identify new potential TcGAPDH inhibitors with trypanocidal activity.
Methods: A virtual screening based on molecular docking of FDA-approved drugs was performed, followed by in vitro biological evaluation of trypomastigotes from two T. cruzi strains.
Results: Seven FDA-approved drugs (pemetrexed, gliquidone, irbesartan, enoxacin, norfloxacin, pazopanib, and fenoprofen) had the best affinity values and a suitable interaction profile at the active site of the TcGAPDH enzyme, which had better LC50 values than the reference drugs.
Discussion: Drug repositioning using computer-aided methods reduces cost and time to find new pharmacological treatments. In this study, gliquidone (antidiabetic), irbesartan (antihypertensive), pemetrexed, and pazopanib (anticancer) are drugs with high trypanocidal activity that could be candidates for evaluation in clinical phases or used to develop new drugs to combat Chagas disease. It highlights fenoprofen, an anti-inflammatory agent, which has biological properties that help to reduce the symptomatology of the disease in the chronic stage. Additionally, it is necessary to study the mechanism of action of these compounds in detail to confirm if they have an effect on the proposed pharmacological targets.
Conclusion: Seven FDA-approved drugs are candidates for further studies leading to the development of potential new treatments for Chagas disease.
期刊介绍：
Aims & Scope
Medicinal Chemistry a peer-reviewed journal, aims to cover all the latest outstanding developments in medicinal chemistry and rational drug design. The journal publishes original research, mini-review articles and guest edited thematic issues covering recent research and developments in the field. Articles are published rapidly by taking full advantage of Internet technology for both the submission and peer review of manuscripts. Medicinal Chemistry is an essential journal for all involved in drug design and discovery.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
