{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T09:16:49Z","timestamp":1764494209600,"version":"build-2065373602"},"reference-count":96,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T00:00:00Z","timestamp":1650326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Deanship of Scientific Research (DSR) at King Abdulaziz University","award":[". (RG-15-166-42)"],"award-info":[{"award-number":[". (RG-15-166-42)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>A series of quinoline\u2013uracil hybrids (10a\u2013l) has been rationalized and synthesized. The inhibitory activity against hCA isoforms I, II, IX, and XII was explored. Compounds 10a\u2013l demonstrated powerful inhibitory activity against all tested hCA isoforms. Compound 10h displayed the best selectivity profile with good activity. Compound 10d displayed the best activity profile with minimal selectivity. Compound 10l emerged as the best congener considering both activity (IC50 = 140 and 190 nM for hCA IX and hCA XII, respectively) and selectivity (S.I. = 13.20 and 9.75 for II\/IX, and II\/XII, respectively). The most active hybrids were assayed for antiproliferative and pro-apoptotic activities against MCF-7 and A549. In silico studies, molecular docking, physicochemical parameters, and ADMET analysis were performed to explain the acquired CA inhibitory action of all hybrids. A study of the structure\u2013activity relationship revealed that bulky substituents at uracil N-1 were unfavored for activity while substituted quinoline and thiouracil were effective for selectivity.<\/jats:p>","DOI":"10.3390\/ph15050494","type":"journal-article","created":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T00:22:43Z","timestamp":1650414163000},"page":"494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Uracil as a Zn-Binding Bioisostere of the Allergic Benzenesulfonamide in the Design of Quinoline\u2013Uracil Hybrids as Anticancer Carbonic Anhydrase Inhibitors"],"prefix":"10.3390","volume":"15","author":[{"given":"Samar A.","family":"El-Kalyoubi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City, Cairo 11651, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1091-2885","authenticated-orcid":false,"given":"Ehab S.","family":"Taher","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3049-4617","authenticated-orcid":false,"given":"Tarek S.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7843-1423","authenticated-orcid":false,"given":"Mohammed Farrag","family":"El-Behairy","sequence":"additional","affiliation":[{"name":"Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City, Menoufiya 32897, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amany M. M.","family":"Al-Mahmoudy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.2174\/138161208783877884","article-title":"Carbonic Anhydrases An Overview","volume":"14","author":"Supuran","year":"2008","journal-title":"Curr. Pharm. Des."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1080\/14756366.2021.1972995","article-title":"An overview on the recently discovered iota-carbonic anhydrases","volume":"36","author":"Nocentini","year":"2021","journal-title":"J. Enzym. Inhib. Med. 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