Design, Synthesis, Molecular Docking Analysis, and Carbonic Anhydrase IX Inhibitory Evaluations of Novel N-Substituted-β-d-Glucosamine Derivatives that Incorporate Benzenesulfonamides

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Feng-Ran LiMao-Sheng Cheng

Abstract

A series of novel N-substituted-β-d-glucosamine derivatives that incorporate benzenesulfonamides were designed using a fragment-based drug design strategy. Each derivative was synthesized and evaluated in vitro for its inhibitory activity against human carbonic anhydrase (hCA) IX; several derivatives displayed desirable potency profiles against this enzyme. The molecular docking studies provided the design rationale and predicted potential binding modes for carbonic anhydrase (CA) IX and three target compounds, including the most potent inhibitor, compound 7f (IC50 = 10.01 nM). Moreover, the calculated Log P (cLog P) values showed that all the compounds tended to be hydrophilic. In addition, topological polar surface area (TPSA) value-based predictions highlighted the selectivity of these carbohydrate-based inhibitors for membrane-associated CA IX.

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Citations

Jul 3, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zuo-Peng ZhangMao-Sheng Cheng
Aug 6, 2019·Bioorganic Chemistry·Begüm Nurpelin SağlıkZafer Asım Kaplancıklı
Jun 3, 2021·International Journal of Molecular Sciences·Zuo-Peng ZhangMao-Sheng Cheng

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column chromatography
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