{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:22:39Z","timestamp":1791606159206,"version":"4.3.4"},"reference-count":39,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Education of Liaoning Province","award":["LJKZ0928"],"award-info":[{"award-number":["LJKZ0928"]}]},{"name":"Department of Education of Liaoning Province","award":["LJKQZ2021036"],"award-info":[{"award-number":["LJKQZ2021036"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In this work, we designed a series of new carbohydrate-based coumarin carbonic anhydrase IX inhibitors by using 1,2,3-triazoles as linker. Next, these designed compounds were synthesized by the optimized one-pot click chemistry reaction condition. Subsequently, these target compounds were assayed for the inhibition of three carbonic anhydrase isoforms (CA I, CA II and CA IX). Intriguingly, all the compounds showed better CA IX inhibitory activity than initial coumarin fragments. Among them, compound 10a (IC50: 11 nM) possessed the most potent CA IX inhibitory activity, which was more potent than the reference drug acetazolamide (IC50: 30 nM). Notably, compound 10a showed 3018-fold, 1955-fold selectivity relative to CA I and CA II, respectively. Meanwhile, representative compounds could reduce tumor cell viability and the extracellular acidification in HT-29 and MDA-MB-231 cancer cell lines. Even more interestingly, our target compounds had no apparent cytotoxicity toward MCF-10A cell line. In addition, the in vitro stability assays also indicated our developed compounds possessed good liver microsomal metabolic stabilities and plasma stability. Furthermore, representative compounds revealed relatively low hERG cardiac toxicity and acute toxicity. Furthermore, docking studies were carried out to understand the interactions of our target compounds with the protein target CA IX. Collectively, our results suggest that compound 10a, as a selective CA IX inhibitor, could be an important lead compound for further optimization and development as an anticancer agent.<\/jats:p>","DOI":"10.3390\/molecules27175464","type":"journal-article","created":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T02:04:32Z","timestamp":1661479472000},"page":"5464","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Design, Synthesis and Biological Evaluation of New Carbohydrate-Based Coumarin Derivatives as Selective Carbonic Anhydrase IX Inhibitors via \u201cClick\u201d Reaction"],"prefix":"10.3390","volume":"27","author":[{"given":"Naying","family":"Chu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The First People\u2019s Hospital of Shangqiu, Suiyang District, 292 Kaixuan Road, Shangqiu 476000, China"},{"name":"China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yitong","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First People\u2019s Hospital of Shangqiu, Suiyang District, 292 Kaixuan Road, Shangqiu 476000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First People\u2019s Hospital of Shangqiu, Suiyang District, 292 Kaixuan Road, Shangqiu 476000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First People\u2019s Hospital of Shangqiu, Suiyang District, 292 Kaixuan Road, Shangqiu 476000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuang","family":"Hou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nrd2467","article-title":"Carbonic anhydrases: Novel therapeutic applications for inhibitors and activators","volume":"7","author":"Supuran","year":"2008","journal-title":"Nat. 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