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

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 H-1 NMR, C-13 NMR, IR, and elemental analysis methods (7g-7l). The antioxidant potencies measured by using CUPRAC method (Trolox equivalent total anti-oxidant 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 alpha-glycosidase enzymes. Compounds 7c, 7e, 7g, 7i, 7j and 7l showed promising human carbonic anhydrase I inhibition compared to the standard Acetazolamide (K-i: 16.64 +/- 4.72-49.82 +/- 5.82 nM vs K-i: 57.64 +/- 5.41 nM). In addition, all compounds exhibited strong inhibition against acetylcholinesterase and a-glycosidase. K-i values were between 2.39 +/- 0.97-9.35 +/- 3.95 nM (Tacrine K-i: 13.78 +/- 4.36 nM) for acetylcholinesterase, and 14.49 +/- 8.51-75.67 +/- 26.38 nM (Acarbose K-i: 12600 +/- 78.00 nM) for a-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.