Design, synthesis and biological evaluation of carbohydrate-based sulphonamide derivatives as topical antiglaucoma agents through selective inhibition of carbonic anhydrase II

Abstract

A series of new carbohydrate-based sulphonamide derivatives were designed, synthesised by employing the so-call ‘sugar-tail’ approach. The compounds were evaluated in vitro against a panel of CAs. Compared to their parent compound p-sulfamoylbenzoic acid, these compounds showed nearly 100-fold improvement in their binding affinities against hCA II in vitro. All of compounds showed great water solubility and the pH value of their water solutions of compounds is 7.0. Such properties are advantageous to make them much less irritating to the eye when applied topical glaucomatous drugs, compared to the relatively highly acidic dorzolamide preparations (pH 5.5). Notably, compounds 7d, 7 g, 7 h demonstrated to topically lower intraocular pressure (IOP) in glaucomatous animals better than brinzolamide when applied as a 1% solution directly into the eye. Low cytotoxicity on human cornea epithelial cell was observed in the tested concentrations by the MTT assay.

Keywords:

• Carbonic anhydrase II inhibitors
• sugar tail
• hydrophilic half
• antiglaucoma

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors appreciate the financial supports from the National Natural Science Foundation of China [No. 81903463], Department of Education of Liaoning Province [2017LQN03] and Department of Science and Technology of Liaoning Province [20180540032].