Extending the scope of amantadine drug by incorporation of phenolic azo Schiff bases as potent selective inhibitors of carbonic anhydrase II, drug-likeness and binding analysis

Abstract

A series of Amantadine-based azo Schiff base dyes 6a-6e have been synthesized and characterized by ¹ H NMR and ¹³ C NMR and evaluated for their in vitro carbonic anhydrase II inhibition activity and antioxidant activity. All of the synthesized showed excellent carbonic inhibition. Compound 6b was found to be the most potent derivative in the series, and the IC₅₀ of 6b was found to be 0.0849 ± 0.00245 μm (standard Acetazolamide IC₅₀ = 0.9975 ± 0.049 μm). The binding interactions of the most active analogs were confirmed through molecular docking studies. Docking studies showed 6b is interacting by making two hydrogen bonds w at His93 and Ser1 residues, respectively. All compounds showed a good drug score and followed Lipinski's rule. In summary, our studies have shown that these amantadine-derived phenolic azo Schiff base derivatives are a new class of carbonic anhydrase II inhibitors.

Keywords: Carbonic anhydrase II inhibition; amantadine drug derivatives; antioxidant; binding analysis; drug score; drug-likeness; phenolic azo Schiff bases.