title: Sulfonamides containing coumarin moieties selectively and potently inhibit carbonic anhydrases II and IX: design, synthesis, inhibitory activity and 3D-QSAR analysis.
abstract: A series of sulfonamides containing coumarin moieties had been prepared that showed a very interesting profile for the inhibition of two human carbonic anhydrase inhibitors. These compounds were evaluated for their ability to inhibit the enzymatic activity of the physiologically dominant isozymes hCA II and the tumor-associated isozyme hCA IX. The most potent inhibitor against hCA II and IX were compounds 5d (IC₅₀ = 23 nM) and 5l (IC₅₀ = 24 nM), respectively. These sulfonamides containing coumarin moieties may prove interesting lead candidates to target tumor-associated CA isozymes, wherein the CA domain is located extracellularly. Eighteen compounds were scrutinized by CoMFA and CoMSIA techniques of 3D quantitative structure-activity relationship. Nine of the compounds were evaluated for cytotoxicity against human macrophage.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Zhong-Chang
authors.initials: ZC
authors.lastname: Wang
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Qin
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Wang
authors.forename: Yong-An
authors.initials: YA
authors.lastname: Yang
authors.forename: Qing
authors.initials: Q
authors.lastname: Wen
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Han-Yue
authors.initials: HY
authors.lastname: Qiu
authors.forename: Yong-Tao
authors.initials: YT
authors.lastname: Duan
authors.forename: Yan-Ting
authors.initials: YT
authors.lastname: Wang
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Sang
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D030741:Carbonic Anhydrase IV / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D060326:Chemistry Techniques, Synthetic; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D061986:MCF-7 Cells; D008546:Melanoma, Experimental; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D013379:Substrate Specificity; D013449:Sulfonamides / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; D003374:Coumarins; D007527:Isoenzymes; D013449:Sulfonamides; C030123:coumarin; D024402:Carbonic Anhydrase II; D030741:Carbonic Anhydrase IV
keywords: 3D-QSAR; Antitumor activity; CCK-8 assay; Carbonic anhydrase; Sulfonamide derivatives