{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T23:35:18Z","timestamp":1793230518270,"version":"4.5.0"},"reference-count":69,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science, Technology &amp; Innovation Funding Authority","award":["43040"],"award-info":[{"award-number":["43040"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sixteen new thalidomide analogs were synthesized. The new candidates showed potent in vitro antiproliferative activities against three human cancer cell lines, namely hepatocellular carcinoma (HepG-2), prostate cancer (PC3), and breast cancer (MCF-7). It was found that compounds XII, XIIIa, XIIIb, XIIIc, XIIId, XIVa, XIVb, and XIVc showed IC50 values ranging from 2.03 to 13.39 \u00b5g\/mL, exhibiting higher activities than thalidomide against all tested cancer cell lines. Compound XIIIa was the most potent candidate, with an IC50 of 2.03 \u00b1 0.11, 2.51 \u00b1 0.2, and 0.82 \u00b1 0.02 \u00b5g\/mL compared to 11.26 \u00b1 0.54, 14.58 \u00b1 0.57, and 16.87 \u00b1 0.7 \u00b5g\/mL for thalidomide against HepG-2, PC3, and MCF-7 cells, respectively. Furthermore, compound XIVc reduced the expression of NF\u03baB P65 levels in HepG-2 cells from 278.1 pg\/mL to 63.1 pg\/mL compared to 110.5 pg\/mL for thalidomide. Moreover, compound XIVc induced an eightfold increase in caspase-8 levels with a simultaneous decrease in TNF-\u03b1 and VEGF levels in HepG-2 cells. Additionally, compound XIVc induced apoptosis and cell cycle arrest. Our results reveal that the new candidates are potential anticancer candidates, particularly XIIIa and XIVc. Consequently, they should be considered for further evaluation for the development of new anticancer drugs.<\/jats:p>","DOI":"10.3390\/ijms241512416","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T09:27:48Z","timestamp":1691141268000},"page":"12416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Design, Synthesis, and Biological Evaluation of New Potential Unusual Modified Anticancer Immunomodulators for Possible Non-Teratogenic Quinazoline-Based Thalidomide Analogs"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2989-4820","authenticated-orcid":false,"given":"Reda","family":"Mabrouk","sequence":"first","affiliation":[{"name":"Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt"},{"name":"Directorate of Health Affairs in Buhaira-Clinical Research Department, Ministry of Health and Population, Damanhour 22511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2597-7419","authenticated-orcid":false,"given":"Abdallah","family":"Abdallah","sequence":"additional","affiliation":[{"name":"Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazem","family":"Mahdy","sequence":"additional","affiliation":[{"name":"Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4648-5184","authenticated-orcid":false,"given":"Samar","family":"El-Kalyoubi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Port Said University, Port Said 42511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9872-3150","authenticated-orcid":false,"given":"Omar","family":"Kamal","sequence":"additional","affiliation":[{"name":"King Abdulaziz University Hospital, King Abdulaziz University, Jeddah 21461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamer","family":"Abdelghany","sequence":"additional","affiliation":[{"name":"Pharmacology & Toxicology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt"},{"name":"Pharmacology & Toxicology Department, Faculty of Pharmacy, Heliopolis University for Sustainable Development, Cairo 11785, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8683-5460","authenticated-orcid":false,"given":"Mohamed","family":"Zayed","sequence":"additional","affiliation":[{"name":"Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt"},{"name":"Pharmaceutical Sciences Department, Fakeeh College for Medical Sciences, Jeddah 21461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1960-0092","authenticated-orcid":false,"given":"Heba","family":"Alshaeri","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Department, Fakeeh College for Medical Sciences, Jeddah 21461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moudi","family":"Alasmari","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Jeddah 21461, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center (KAIMRC), Jeddah 21423, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4538-5840","authenticated-orcid":false,"given":"Mohamed","family":"El-Zahabi","sequence":"additional","affiliation":[{"name":"Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3424","DOI":"10.1038\/s41598-022-07456-1","article-title":"Synthesis, and docking studies of novel heterocycles incorporating the indazolylthiazole moiety as antimicrobial and anticancer agents","volume":"12","author":"Dawoud","year":"2022","journal-title":"Sci. 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