Ebtehal M Husseiny, Hamada S Abulkhair, Samiha A El-Sebaey, Manal M Sayed, Kurls E Anwer
{"title":"作为 CDK9 抑制剂的新型合成吡唑酮的体内评价，其药代动力学特性得到增强。","authors":"Ebtehal M Husseiny, Hamada S Abulkhair, Samiha A El-Sebaey, Manal M Sayed, Kurls E Anwer","doi":"10.1080/17568919.2024.2419363","DOIUrl":null,"url":null,"abstract":"<p><p><b>Aim:</b> The structural optimization of our recently reported CDK9 inhibitor to furnish novel aminopyrazolones and methylpyrazolones with improved pharmacokinetics.<b>Materials & methods:</b> The synthesis of the targeted compounds was accomplished via conventional, grinding and microwave-assisted processes. The cytotoxicity of them was assayed against three carcinomas.<b>Results:</b> Analogs <b>2</b>, <b>4</b> and <b>6</b> showed significant cytotoxicity and selectivity toward all tested cells. They also displayed potent CDK9 inhibition. Compound <b>6</b> arrested MCF-7 cycle at G2/M phase by stimulating the apoptotic pathway. The <i>in vivo</i> biodistribution of radiolabeled compound <b>6</b> displayed a potent targeting capability of <sup>131</sup>I in solid tumors.<b>Conclusion:</b> Entity <b>6</b> is a potent CDK9 inhibitor where <sup>131</sup>I-compound <b>6</b> can be used as a significant radiopharmaceutical imaging tool for tumors.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"<i>In vivo</i> evaluation of novel synthetic pyrazolones as CDK9 inhibitors with enhanced pharmacokinetic properties.\",\"authors\":\"Ebtehal M Husseiny, Hamada S Abulkhair, Samiha A El-Sebaey, Manal M Sayed, Kurls E Anwer\",\"doi\":\"10.1080/17568919.2024.2419363\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Aim:</b> The structural optimization of our recently reported CDK9 inhibitor to furnish novel aminopyrazolones and methylpyrazolones with improved pharmacokinetics.<b>Materials & methods:</b> The synthesis of the targeted compounds was accomplished via conventional, grinding and microwave-assisted processes. The cytotoxicity of them was assayed against three carcinomas.<b>Results:</b> Analogs <b>2</b>, <b>4</b> and <b>6</b> showed significant cytotoxicity and selectivity toward all tested cells. They also displayed potent CDK9 inhibition. Compound <b>6</b> arrested MCF-7 cycle at G2/M phase by stimulating the apoptotic pathway. The <i>in vivo</i> biodistribution of radiolabeled compound <b>6</b> displayed a potent targeting capability of <sup>131</sup>I in solid tumors.<b>Conclusion:</b> Entity <b>6</b> is a potent CDK9 inhibitor where <sup>131</sup>I-compound <b>6</b> can be used as a significant radiopharmaceutical imaging tool for tumors.</p>\",\"PeriodicalId\":12475,\"journal\":{\"name\":\"Future medicinal chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-11-12\",\"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/10.1080/17568919.2024.2419363\",\"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":"Future medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17568919.2024.2419363","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
In vivo evaluation of novel synthetic pyrazolones as CDK9 inhibitors with enhanced pharmacokinetic properties.
Aim: The structural optimization of our recently reported CDK9 inhibitor to furnish novel aminopyrazolones and methylpyrazolones with improved pharmacokinetics.Materials & methods: The synthesis of the targeted compounds was accomplished via conventional, grinding and microwave-assisted processes. The cytotoxicity of them was assayed against three carcinomas.Results: Analogs 2, 4 and 6 showed significant cytotoxicity and selectivity toward all tested cells. They also displayed potent CDK9 inhibition. Compound 6 arrested MCF-7 cycle at G2/M phase by stimulating the apoptotic pathway. The in vivo biodistribution of radiolabeled compound 6 displayed a potent targeting capability of 131I in solid tumors.Conclusion: Entity 6 is a potent CDK9 inhibitor where 131I-compound 6 can be used as a significant radiopharmaceutical imaging tool for tumors.
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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