Synthesis, Docking Study and Biological Activities Evaluation of 1‐Amidoalkyl‐2‐naphthol Derivatives as Dual Inhibitors of Cholinesterase and α‐Glucosidase

Abstract An efficient green synthesis of 1‐amidoalkyl‐2‐naphthol derivatives 4 a‐s has been developed, employing phenylboronic acid, by a three component one‐pot condensation reaction of 2‐naphthol, a wide range of functionalized aromatic aldehydes and acetamide, or acrylamide under solvent‐free conditions. This new protocol has the rewards of ecologically benign, easy workup along with good to excellent yields. Moreover, selected compounds were screened towards inhibition of cholinesterase. In vitro studies showed that some synthesized compounds have significant both AChE and BChE inhibitory activities compared to Galanthamine (reference drug). Compounds 4 p and 4 s were the most effective showing high potential AChE and BChE inhibitory activities with respective IC 50 values of 13.81±0.54 μM and 31.70±1.29 μM. Subsequent evaluation of the α‐glucosidase inhibitory activity of the target molecules revealed that compound 4 s with an IC 50 value of 2.05±0.05 μM exhibited highest activity. These preliminary results provide promising sources of multifunctional agents and sheds light on their potential usage in medicine and in the pharmaceutical industries. Using molecular docking approach, we tried to get insights into binding interactions of our synthesized compounds to act as AChE and BChE inhibitors and understand the facts that underlie the relationships between structural modifications on these ligands and their efficacy.