Reda G Yousef, Ibrahim H Eissa, Hazem Elkady, Ahmed B M Mehany, Mariam Ali Abo-Saif, Mohamed M Radwan, Mahmoud A ElSohly, Ibrahim M Ibrahim, Alaa Elwan, Mohamed Ayman El-Zahabi
{"title":"作为免疫调节 VEGFR-2 抑制剂和细胞凋亡诱导剂的新型烟酰胺的设计与合成。","authors":"Reda G Yousef, Ibrahim H Eissa, Hazem Elkady, Ahmed B M Mehany, Mariam Ali Abo-Saif, Mohamed M Radwan, Mahmoud A ElSohly, Ibrahim M Ibrahim, Alaa Elwan, Mohamed Ayman El-Zahabi","doi":"10.1080/17568919.2024.2421150","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background:</b> Nicotinamide-based VEGFR-2 inhibitors have good contribution in drug discovery.<b>Aim:</b> Development of novel nicotinamides as VEGFR-2 inhibitors.<b>Methods:</b> different <i>in vitro</i> and <i>in silico</i> assays were conducted to evaluate the VEGFR-2 inhibition and cytotoxicity.<b>Results:</b> Compound <b>16c</b> displayed strongest anti-VEGFR-2 potentiality and good anti-proliferative effects. Compound <b>16c</b> enhanced apoptosis and caused cell cycle arrest in the Pre-G1 and S phases. Compound <b>16c</b> boosted the level of the apoptotic caspase-3 and inhibited the level of TNF-α and IL-6 in tumor cells. Molecular docking and molecular dynamics (MD) simulations indicated the outstanding binding potential of compound <b>16c</b> against VEGFR-2.<b>Conclusion:</b> Compound <b>16c</b> is a good candidate for the creation of a novel antiangiogenic lead anticancer medication.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Design and synthesis of new nicotinamides as immunomodulatory VEGFR-2 inhibitors and apoptosis inducers.\",\"authors\":\"Reda G Yousef, Ibrahim H Eissa, Hazem Elkady, Ahmed B M Mehany, Mariam Ali Abo-Saif, Mohamed M Radwan, Mahmoud A ElSohly, Ibrahim M Ibrahim, Alaa Elwan, Mohamed Ayman El-Zahabi\",\"doi\":\"10.1080/17568919.2024.2421150\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Background:</b> Nicotinamide-based VEGFR-2 inhibitors have good contribution in drug discovery.<b>Aim:</b> Development of novel nicotinamides as VEGFR-2 inhibitors.<b>Methods:</b> different <i>in vitro</i> and <i>in silico</i> assays were conducted to evaluate the VEGFR-2 inhibition and cytotoxicity.<b>Results:</b> Compound <b>16c</b> displayed strongest anti-VEGFR-2 potentiality and good anti-proliferative effects. Compound <b>16c</b> enhanced apoptosis and caused cell cycle arrest in the Pre-G1 and S phases. Compound <b>16c</b> boosted the level of the apoptotic caspase-3 and inhibited the level of TNF-α and IL-6 in tumor cells. Molecular docking and molecular dynamics (MD) simulations indicated the outstanding binding potential of compound <b>16c</b> against VEGFR-2.<b>Conclusion:</b> Compound <b>16c</b> is a good candidate for the creation of a novel antiangiogenic lead anticancer medication.</p>\",\"PeriodicalId\":12475,\"journal\":{\"name\":\"Future medicinal chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-11-14\",\"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/10.1080/17568919.2024.2421150\",\"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/10.1080/17568919.2024.2421150","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Design and synthesis of new nicotinamides as immunomodulatory VEGFR-2 inhibitors and apoptosis inducers.
Background: Nicotinamide-based VEGFR-2 inhibitors have good contribution in drug discovery.Aim: Development of novel nicotinamides as VEGFR-2 inhibitors.Methods: different in vitro and in silico assays were conducted to evaluate the VEGFR-2 inhibition and cytotoxicity.Results: Compound 16c displayed strongest anti-VEGFR-2 potentiality and good anti-proliferative effects. Compound 16c enhanced apoptosis and caused cell cycle arrest in the Pre-G1 and S phases. Compound 16c boosted the level of the apoptotic caspase-3 and inhibited the level of TNF-α and IL-6 in tumor cells. Molecular docking and molecular dynamics (MD) simulations indicated the outstanding binding potential of compound 16c against VEGFR-2.Conclusion: Compound 16c is a good candidate for the creation of a novel antiangiogenic lead anticancer medication.
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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