Discovery of new potent inhibitors for carbonic anhydrase IX by structure-based virtual screening |
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Authors: | Liyan Wang Chunmei Yang Weiqiang Lu Li Liu Rui Gao Sha Liao Zhenjiang Zhao Lili Zhu Yufang Xu Honglin Li Jin Huang Weiping Zhu |
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Institution: | State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China |
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Abstract: | Through structure-based virtual screening, some dozen of benzene sulfonamides with novel scaffolds are identified as potent inhibitors against carbonic anhydrase (CA) IX with IC50 values ranging from 2.86 to 588.34 nM. Among them, compounds 1 and 9 show high selectivity against tumor-target CA IX over CA II (the selectivity ratios are 21.3 and 136.6, respectively). The possible binding poses of hit compounds are also explored and the selectivity is elucidated by molecular docking simulations. The hit compounds discovered in this work would provide novel scaffolds for further hit-to-lead optimization. |
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Keywords: | Virtual screening Molecular docking Carbonic anhydrase inhibitors Sulfonamides |
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