{"title":"Discovery of 1,5-diaryl-1,2,4-triazole derivatives as myoferlin inhibitors and their antitumor effects in pancreatic cancer.","authors":"Haijun Gu, Ting Zhang, Yunqi Li, Yuan He, Tian Guan, Weiqiong Kan, Peng He, Zhengfang Yi, Yihua Chen","doi":"10.4155/fmc-2022-0168","DOIUrl":null,"url":null,"abstract":"<p><p><b>Aim:</b> The first inhibitor targeting myoferlin (MYOF), <b>WJ460</b>, bears poor metabolic stability and water solubility. Therefore, this study aimed to improve the drug-like properties of <b>WJ460</b>. <b>Materials & methods:</b> The authors synthesized an array of 1,5-diaryl-1,2,4-triazole analogs and appraised the binding activities with MYOF and their antiproliferative and antimigratory activities against pancreatic cancer cells. <b>Results:</b> Molecular docking and surface plasmon resonance results showed that <b>E4</b> was directly bound to the MYOF-C2D domain. <b>E4</b> effectively inhibited the proliferation and migration of pancreatic cancer cells <i>in vitro</i>. An <i>in silico</i> study suggested that the water solubility of <b>E4</b> was improved by about 22-times than that of <b>WJ460</b>. <b>Conclusion:</b> The findings suggested that the druglike ability of <b>E4</b> was significantly improved.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":"14 20","pages":"1425-1440"},"PeriodicalIF":3.2000,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Future medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4155/fmc-2022-0168","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/9/27 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Aim: The first inhibitor targeting myoferlin (MYOF), WJ460, bears poor metabolic stability and water solubility. Therefore, this study aimed to improve the drug-like properties of WJ460. Materials & methods: The authors synthesized an array of 1,5-diaryl-1,2,4-triazole analogs and appraised the binding activities with MYOF and their antiproliferative and antimigratory activities against pancreatic cancer cells. Results: Molecular docking and surface plasmon resonance results showed that E4 was directly bound to the MYOF-C2D domain. E4 effectively inhibited the proliferation and migration of pancreatic cancer cells in vitro. An in silico study suggested that the water solubility of E4 was improved by about 22-times than that of WJ460. Conclusion: The findings suggested that the druglike ability of E4 was significantly improved.
期刊介绍：
Future Medicinal Chemistry offers a forum for the rapid publication of original research and critical reviews of the latest milestones in the field. Strong emphasis is placed on ensuring that the journal stimulates awareness of issues that are anticipated to play an increasingly central role in influencing the future direction of pharmaceutical chemistry. Where relevant, contributions are also actively encouraged on areas as diverse as biotechnology, enzymology, green chemistry, genomics, immunology, materials science, neglected diseases and orphan drugs, pharmacogenomics, proteomics and toxicology.
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