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.

Synthesis, Bioactivity Assessment, and Molecular Docking of Non-sulfonamide Benzimidazole-Derived N-Acylhydrazone Scaffolds as Carbonic Anhydrase-II Inhibitors

“…The chemical synthesis given below was performed according to the reported methods. 19,20 Synthesis of 2-(Propylthio)-1H-benzo [d]imidazole (3). A total of 133 mmol (20 g) 2-MBI (1) was taken in an RB flask in 40 mL of ethanol, to which 133 mmol (7.5 g) KOH was added and heated over a magnetic hotplate stirrer.…”

“…Their abnormal levels result in glaucoma and edema. Many CA inhibitors (CAIs) mostly belong to the sulfonamide class such as benzimidazole-6-sulfonamides, acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, benzenesulfonamide, and so forth. − …”

An overview of carbohydrate-based carbonic anhydrase inhibitors

“…In 2020 a new series of carbohydrate-based sulfonamides was reported (compounds 124 – 131 , Figure 7 ) 33 . The conjugation was achieved with a classical amide bond between the proper aminosugar and the p -sulfamoyl benzoic acid.…”

Screening of Carbonic Anhydrase, Acetylcholinesterase, Butyrylcholinesterase, and α-Glycosidase Enzyme Inhibition Effects and Antioxidant Activity of Coumestrol

“…It is also estimated that the number of glaucoma patients worldwide will rise to 112 million by 2040 [ 36 ]. Glaucoma is an ophthalmologic disorder characterized by high intraocular pressure (IOP) that eventually causes irreversible peripheral vision loss and eventually blindness [ 37 , 38 , 39 , 40 ]. Clinically, there are many methods for treatment of glaucoma such as laser, surgery, and pharmacological therapies.…”