Sayonara Maria Calado Gonçalves, Lília Vieira Galdino, Morganna Costa Lima, José Arion da Silva Moura, Douglas Carvalho Francisco Viana, Michelle Melgarejo da Rosa, Luiz Felipe Gomes Rebello Ferreira, Marcelo Zaldini Hernandes, Michelly Cristiny Pereira, Moacyr Jesus Barreto de Melo Rêgo, Ivan da Rocha Pitta, Rafael de Oliveira França, Marina Galdino da Rocha Pitta, Maira Galdino da Rocha Pitta
{"title":"评估具有潜在抗 ZIKV 活性的噻唑烷衍生物","authors":"Sayonara Maria Calado Gonçalves, Lília Vieira Galdino, Morganna Costa Lima, José Arion da Silva Moura, Douglas Carvalho Francisco Viana, Michelle Melgarejo da Rosa, Luiz Felipe Gomes Rebello Ferreira, Marcelo Zaldini Hernandes, Michelly Cristiny Pereira, Moacyr Jesus Barreto de Melo Rêgo, Ivan da Rocha Pitta, Rafael de Oliveira França, Marina Galdino da Rocha Pitta, Maira Galdino da Rocha Pitta","doi":"10.2174/0115680266315388240801053401","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>In this study, we have synthesized 19 Thiazolidine (TZD) derivatives to investigate their potential anti-ZIKV effects.</p><p><strong>Methods: </strong>Nineteen thiazolidine derivatives were synthesized and evaluated for their cytotoxicity and antiviral activity against the ZIKA virus.</p><p><strong>Results: </strong>Among them, six demonstrated remarkable selectivity against the ZIKV virus, exhibiting IC50 values of <5μM, and the other compounds did not demonstrate selectivity for the virus. Interestingly, several derivatives effectively suppressed the replication of ZIKV RNA copies, with derivatives significantly reducing ZIKV mRNA levels at 24 hours post-infection (hpi). Notably, two derivatives (ZKC-4 and -9) stood out by demonstrating a protective effect against ZIKV cell entry. Informed by computational analysis of binding affinity and intermolecular interactions within the NS5 domain's N-7 and O'2 positions, ZKC-4 and FT-39 displayed the highest predicted affinities. Intriguingly, ZKC-4 and ZKC-9 derivatives exhibited the most favorable predicted binding affinities for the ZIKV-E binding site.</p><p><strong>Conclusion: </strong>The significance of TZDs as potent antiviral agents is underscored by these findings, suggesting that exploring TZD derivatives holds promise for advancing antiviral therapeutic strategies.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":"2224-2237"},"PeriodicalIF":2.9000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Evaluation of Thiazolidine Derivatives with Potential Anti-ZIKV Activity.\",\"authors\":\"Sayonara Maria Calado Gonçalves, Lília Vieira Galdino, Morganna Costa Lima, José Arion da Silva Moura, Douglas Carvalho Francisco Viana, Michelle Melgarejo da Rosa, Luiz Felipe Gomes Rebello Ferreira, Marcelo Zaldini Hernandes, Michelly Cristiny Pereira, Moacyr Jesus Barreto de Melo Rêgo, Ivan da Rocha Pitta, Rafael de Oliveira França, Marina Galdino da Rocha Pitta, Maira Galdino da Rocha Pitta\",\"doi\":\"10.2174/0115680266315388240801053401\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>In this study, we have synthesized 19 Thiazolidine (TZD) derivatives to investigate their potential anti-ZIKV effects.</p><p><strong>Methods: </strong>Nineteen thiazolidine derivatives were synthesized and evaluated for their cytotoxicity and antiviral activity against the ZIKA virus.</p><p><strong>Results: </strong>Among them, six demonstrated remarkable selectivity against the ZIKV virus, exhibiting IC50 values of <5μM, and the other compounds did not demonstrate selectivity for the virus. Interestingly, several derivatives effectively suppressed the replication of ZIKV RNA copies, with derivatives significantly reducing ZIKV mRNA levels at 24 hours post-infection (hpi). Notably, two derivatives (ZKC-4 and -9) stood out by demonstrating a protective effect against ZIKV cell entry. Informed by computational analysis of binding affinity and intermolecular interactions within the NS5 domain's N-7 and O'2 positions, ZKC-4 and FT-39 displayed the highest predicted affinities. Intriguingly, ZKC-4 and ZKC-9 derivatives exhibited the most favorable predicted binding affinities for the ZIKV-E binding site.</p><p><strong>Conclusion: </strong>The significance of TZDs as potent antiviral agents is underscored by these findings, suggesting that exploring TZD derivatives holds promise for advancing antiviral therapeutic strategies.</p>\",\"PeriodicalId\":11076,\"journal\":{\"name\":\"Current topics in medicinal chemistry\",\"volume\":\" \",\"pages\":\"2224-2237\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current topics in medicinal chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/0115680266315388240801053401\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current topics in medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115680266315388240801053401","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Evaluation of Thiazolidine Derivatives with Potential Anti-ZIKV Activity.
Objective: In this study, we have synthesized 19 Thiazolidine (TZD) derivatives to investigate their potential anti-ZIKV effects.
Methods: Nineteen thiazolidine derivatives were synthesized and evaluated for their cytotoxicity and antiviral activity against the ZIKA virus.
Results: Among them, six demonstrated remarkable selectivity against the ZIKV virus, exhibiting IC50 values of <5μM, and the other compounds did not demonstrate selectivity for the virus. Interestingly, several derivatives effectively suppressed the replication of ZIKV RNA copies, with derivatives significantly reducing ZIKV mRNA levels at 24 hours post-infection (hpi). Notably, two derivatives (ZKC-4 and -9) stood out by demonstrating a protective effect against ZIKV cell entry. Informed by computational analysis of binding affinity and intermolecular interactions within the NS5 domain's N-7 and O'2 positions, ZKC-4 and FT-39 displayed the highest predicted affinities. Intriguingly, ZKC-4 and ZKC-9 derivatives exhibited the most favorable predicted binding affinities for the ZIKV-E binding site.
Conclusion: The significance of TZDs as potent antiviral agents is underscored by these findings, suggesting that exploring TZD derivatives holds promise for advancing antiviral therapeutic strategies.
期刊介绍：
Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.
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