{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:05:31Z","timestamp":1787241931697,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,9,3]],"date-time":"2022-09-03T00:00:00Z","timestamp":1662163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    A novel series of 2\u2010thioquinazoline\u2010benzenesulfonamide hybrids were designed as carbonic anhydrase (CA) inhibitors. The design approach relies on molecular hybridization between the benzenesulfonamide scaffold as a Zn\n                    <jats:sup>2+<\/jats:sup>\n                    binding group and 2\u2010substituted thioquinazolines as a tail. Assaying the thioquinazoline\u2010benzenesulfonamide conjugates against four different CA isoforms revealed that compounds\n                    <jats:bold>12f<\/jats:bold>\n                    and\n                    <jats:bold>12p<\/jats:bold>\n                    are the most potent derivatives. They exhibit\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>i<\/jats:sub>\n                    \u2009=\u20090.09 and 0.05\u2009\u00b5M on CA II, 0.32 and 0.47\u2009\u00b5M on CA IX, and 0.58 and 0.46\u2009\u00b5M on CA XII, respectively. In addition,\n                    <jats:bold>12p<\/jats:bold>\n                    demonstrated high selectivity for CA II over CA I with selectivity index (\n                    <jats:italic>SI<\/jats:italic>\n                    )\u2009=\u200992, and slightly higher specificity for CA II over CA IX and CA XII with\n                    <jats:italic>SI<\/jats:italic>\n                    \u2009=\u20099.40 and 9.20, respectively. The synthesized compounds were screened for their cytotoxic activity at 10\u2009\u00b5M concentration and derivatives\n                    <jats:bold>12o<\/jats:bold>\n                    ,\n                    <jats:bold>12n<\/jats:bold>\n                    , and\n                    <jats:bold>12f<\/jats:bold>\n                    turned out to be the most potent ones from the synthesized series; they exhibit mean growth inhibition % values of 89.38%, 58.75%, and 54.71%, respectively, while\n                    <jats:bold>12p<\/jats:bold>\n                    demonstrated moderate activity against the NCI cancer cell lines, with mean growth inhibition %\u2009=\u200929.62%. The analysis of the MCF\u20107 cell cycle after treatment with 5.0\u2009\u00b5M of\n                    <jats:bold>12f<\/jats:bold>\n                    displayed that it arrests the cell cycle at the G2\/M phase. Molecular docking simulation of the thioquinazoline\u2010benzenesulfonamide hybrids in the CA II active site rationalized the potent activity to the settlement of the sulfonamide moiety at the depth of the CA II active site and its stabilization by performing the important interactions with the Zn\n                    <jats:sup>2+<\/jats:sup>\n                    ion as well as with the key amino acids Thr199 and\/or Thr200, while the thioquinazoline moiety with different (un)substituted phenyl tails is stabilized by the formation of various hydrogen bonding and hydrophobic interactions with the surrounding amino acids in the binding site.\n                  <\/jats:p>","DOI":"10.1002\/ardp.202200180","type":"journal-article","created":{"date-parts":[[2022,9,3]],"date-time":"2022-09-03T09:46:17Z","timestamp":1662198377000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Novel 2\u2010substituted thioquinazoline\u2010benzenesulfonamide derivatives as carbonic anhydrase inhibitors with potential anticancer activity"],"prefix":"10.1002","volume":"355","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7610-8312","authenticated-orcid":false,"given":"Heba T.","family":"Abdel\u2010Mohsen","sequence":"first","affiliation":[{"name":"Department of Chemistry of Natural and Microbial Products Pharmaceutical and Drug Industries Research Institute, National Research Centre  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A.","family":"Omar","sequence":"additional","affiliation":[{"name":"Department of Chemistry of Natural and Microbial Products Pharmaceutical and Drug Industries Research Institute, National Research Centre  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Petreni","sequence":"additional","affiliation":[{"name":"Department NEUROFARBA\u2014Pharmaceutical and Nutraceutical Section University of Firenze  Firenze Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4262-0323","authenticated-orcid":false,"given":"Claudiu T.","family":"Supuran","sequence":"additional","affiliation":[{"name":"Department NEUROFARBA\u2014Pharmaceutical and Nutraceutical Section University of Firenze  Firenze Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21654"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cancerbio-030518-055645"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1967.47.4.595"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(96)00198-2"},{"key":"e_1_2_7_7_1","first-page":"3","volume-title":"Carbonic","author":"Supuran C. 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