2. Academic Validation
  3. Sulfonamides containing coumarin moieties selectively and potently inhibit carbonic anhydrases II and IX: design, synthesis, inhibitory activity and 3D-QSAR analysis

Sulfonamides containing coumarin moieties selectively and potently inhibit carbonic anhydrases II and IX: design, synthesis, inhibitory activity and 3D-QSAR analysis

  • Eur J Med Chem. 2013 Aug:66:1-11. doi: 10.1016/j.ejmech.2013.04.035.
Zhong-Chang Wang 1,  Ya-Juan Qin,  Peng-Fei Wang,  Yong-An Yang,  Qing Wen,  Xin Zhang,  Han-Yue Qiu,  Yong-Tao Duan,  Yan-Ting Wang,  Ya-Li Sang,  Hai-Liang Zhu
Affiliations

Affiliation

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
PMID: 23777898 DOI: 10.1016/j.ejmech.2013.04.035
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.

Keywords

3D-QSAR; Antitumor activity; CCK-8 assay; Carbonic anhydrase; Sulfonamide derivatives.

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