{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T13:03:49Z","timestamp":1773493429369,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"published-print":{"date-parts":[[2025,12]]},"abstract":"ABSTRACT<\/jats:title>\n \n Carbonic anhydrases (CAs) are metalloenzymes present in both prokaryotes and eukaryotes, catalyzing the reversible conversion of carbon dioxide and water into bicarbonate ions and protons. Among the various isoforms of CA, human CA (hCA) IX and hCA XII play a critical role in regulating the intracellular and extracellular pH of hypoxic tumor cells. In the present work, we designed and synthesized a series of 4\u2010substituted coumarin derivatives as potent hCA inhibitors. In this study, we synthesized two series of 4\u2010substituted coumarin derivatives (\n 7a\u2013j<\/jats:bold>\n and\n 8a\u2013j<\/jats:bold>\n ) designed as selective inhibitors of these tumor\u2010associated isoforms. All compounds demonstrated selective inhibition of hCA\u00a0IX and hCA\u00a0XII, with K\n i<\/jats:sub>\n values ranging from\n 0.32<\/jats:bold>\n to\n 8.77<\/jats:bold>\n \u00a0\u00b5M. Among them,\n 7c<\/jats:bold>\n and\n 7d<\/jats:bold>\n from the first series exhibited the good activity, with K\n i<\/jats:sub>\n values of\n 0.63<\/jats:bold>\n and\n 0.32<\/jats:bold>\n \u00a0\u00b5M against hCA\u00a0IX, and\n 1.78<\/jats:bold>\n and\n 1.20<\/jats:bold>\n \u00a0\u00b5M against hCA\u00a0XII, respectively; similarly, in the second series,\n 8b<\/jats:bold>\n and\n 8j<\/jats:bold>\n displayed good activity, with K\n i<\/jats:sub>\n values of\n 0.48<\/jats:bold>\n and\n 0.61<\/jats:bold>\n \u00a0\u00b5M against hCA\u00a0IX, and\n 0.66<\/jats:bold>\n and\n 0.96<\/jats:bold>\n \u00a0\u00b5M against hCA\u00a0XII. Molecular docking studies were performed for all synthesized molecules to investigate their binding modes, and molecular dynamics simulations of 200\u00a0ns for selected compounds\n 7c<\/jats:bold>\n and\n 8b<\/jats:bold>\n further confirmed the stability of their complexes within the active sites of hCA\u00a0IX and hCA\u00a0XII.\n <\/jats:p>","DOI":"10.1002\/cbdv.202501800","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T18:51:04Z","timestamp":1756493464000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploration of Novel 4\u2010substituted Coumarin Derivatives as Selective Human Carbonic Anhydrase IX and XII Inhibitors: Synthesis, Biological Evaluation, and In Silico Studies"],"prefix":"10.1002","volume":"22","author":[{"given":"Preeti","family":"Rana","sequence":"first","affiliation":[{"name":"Department of Chemical Science National Institute of Pharmaceutical Education and Research (NIPER) Hyderabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manchella Sai","family":"Supriya","sequence":"additional","affiliation":[{"name":"Department of Chemical Science National Institute of Pharmaceutical Education and Research (NIPER) Hyderabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danaboina","family":"Srikanth","sequence":"additional","affiliation":[{"name":"Department of Chemical Science National Institute of Pharmaceutical Education and Research (NIPER) Hyderabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Ammara","sequence":"additional","affiliation":[{"name":"Neurofarba Dept. Universit\u00e0 Degli Studi Di Firenze Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruturaj","family":"Warake","sequence":"additional","affiliation":[{"name":"Department of Chemical Science National Institute of Pharmaceutical Education and Research (NIPER) Hyderabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hrituja","family":"Gandhe","sequence":"additional","affiliation":[{"name":"Department of Chemical Science National Institute of Pharmaceutical Education and Research (NIPER) Hyderabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venkata Madhavi","family":"Yaddanapudi","sequence":"additional","affiliation":[{"name":"Department of Chemical Science National Institute of Pharmaceutical Education and Research (NIPER) Hyderabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudiu T.","family":"Supuran","sequence":"additional","affiliation":[{"name":"Neurofarba Dept. Universit\u00e0 Degli Studi Di Firenze Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6671-2022","authenticated-orcid":false,"given":"Srinivas","family":"Nanduri","sequence":"additional","affiliation":[{"name":"Department of Chemical Science National Institute of Pharmaceutical Education and Research (NIPER) Hyderabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.135890"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2467"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2022.2052868"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2014.08.002"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2010.05.009"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.15.71"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmcr.2024.100131"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112923"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2023.129411"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm901287j"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2020.1788009"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057108315739"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2023.2185760"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112897"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2019.02.004"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202000915"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.11.061"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2021.127877"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(18)62326\u20109"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3109\/14756366.2013.879656"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm501314c"},{"key":"e_1_2_8_23_1","volume-title":"Schr\u00f6dinger Release 2022\u20101: LigPrep","year":"2021"}],"container-title":["Chemistry & Biodiversity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.202501800","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbdv.202501800","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.202501800","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T11:44:52Z","timestamp":1773488692000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbdv.202501800"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,29]]},"references-count":22,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/cbdv.202501800"],"URL":"https:\/\/doi.org\/10.1002\/cbdv.202501800","archive":["Portico"],"relation":{},"ISSN":["1612-1872","1612-1880"],"issn-type":[{"value":"1612-1872","type":"print"},{"value":"1612-1880","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,29]]},"assertion":[{"value":"2025-05-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01800"}}