Novel coumarin-chalcone derivatives: Synthesis, characterization, antioxidant, cyclic voltammetry, molecular modelling and biological evaluation studies as acetylcholinesterase, α-glycosidase, and carbonic anhydrase inhibitors

Abstract

In this study, a total of 12 coumarin-chalcone derivatives, 6 of which are original were synthesized. The structures of the newly synthesized compounds were elucidated by 1H NMR, 13C NMR, IR, and elemental analysis methods (7g-7l). The antioxidant potencies measured by using CUPRAC method (Trolox equivalent total antioxidant capacity) were as follows: 7j > 7i > 7c > 7d > 7k > 7l > 7f > 7h > 7e > 7g > 7a >7b. Furthermore, the compounds were evaluated against human carbonic anhydrases I, II, acetylcholinesterase and α-glycosidase enzymes. Compounds 7c, 7e, 7g, 7i, 7j and 7l showed promising human carbonic anhydrase I inhibition compared to the standard Acetazolamide (Ki: 16.64 ± 4.72–49.82 ± 5.82 nM vs Ki: 57.64 ± 5.41 nM). In addition, all compounds exhibited strong inhibition against acetylcholinesterase and α-glycosidase. Ki values were between 2.39 ± 0.97–9.35 ± 3.95 nM (Tacrine Ki: 13.78 ± 4.36 nM) for acetylcholinesterase, and 14.49 ± 8.51–75.67 ± 26.38 nM (Acarbose Ki: 12600 ± 78.00 nM) for α-glycosidase. Binding of 7g was predicted using molecular docking and stability of the complex was confirmed with molecular dynamics simulations which shed a light on the observed activity against acetylcholinesterase. Finally, cyclic voltammetry was also used for the electrochemical characterization of the synthesized compounds.