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The biological results revealed the strong impact of quinazoline derivatives <jats:bold>7\u2009a<\/jats:bold> and <jats:bold>28<\/jats:bold>, and phthalazine based <jats:bold>20\u2009a<\/jats:bold> against HepG\u20102, MCF\u20107, PC3, and HCT\u2010116\u2005cell lines, compared to thalidomide. In particular, compound <jats:bold>20\u2009a<\/jats:bold> was the most promising as it had far better biological activity than thalidomide with regard to inhibition of TNF\u2010<jats:italic>\u03b1<\/jats:italic>, IL\u20106, caspase 3, COX\u2010I\/II, and VEGFR\u20102, as well as cell cycle arrest, and apoptosis rate enhancement in MCF\u20107 cells, the most sensitive cell line to the current new molecules. Compound <jats:bold>20\u2009a<\/jats:bold> caused reduction in levels of TNF\u2010<jats:italic>\u03b1<\/jats:italic> and IL\u20106 by 75.22\u2009% and 82.51\u2009%, respectively. It elevated the caspase\u20103 level by 7.21\u2010fold. Furthermore, IC<jats:sub>50<\/jats:sub> against COX\u2010I, COX\u2010II, and VEGFR\u20102 were 0.65\u2005\u03bcM, 0.33\u2005\u03bcM, and 232\u2005nM, respectively. In addition, it raised the apoptosis rate from 65.65\u2009% to 99.89\u2009%. Moreover, <jats:bold>20\u2009a<\/jats:bold> was further examined through a docking study and a 200\u2005ns molecular dynamics simulation for its complex with VEGFR\u20102, along with computational ADME properties. This work suggests the high significance of compounds <jats:bold>20\u2009a<\/jats:bold>, <jats:bold>7\u2009a<\/jats:bold> and <jats:bold>28<\/jats:bold>, as lead compounds for development of new effective immunomodulatory antitumor drugs.<\/jats:p>","DOI":"10.1002\/cbdv.202401768","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T09:14:03Z","timestamp":1731575643000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Discovery of New Immunomodulatory Anticancer Thalidomide Analogs: Design, Synthesis, Biological Evaluation and <i>In Silico<\/i> Studies"],"prefix":"10.1002","volume":"22","author":[{"given":"Abdallah E.","family":"Abdallah","sequence":"first","affiliation":[{"name":"Pharmaceutical Medicinal Chemistry &amp; Drug Design Department, Faculty of Pharmacy (Boys) Al-Azhar University  Cairo 11884 Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim H.","family":"Eissa","sequence":"additional","affiliation":[{"name":"Pharmaceutical Medicinal Chemistry &amp; Drug Design Department, Faculty of Pharmacy (Boys) Al-Azhar University  Cairo 11884 Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed B. 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