Synthesis, molecular docking and cholinesterase inhibitory activity of hydroxylated 2-phenylbenzofuran derivatives

Antonella Fais

First

;Amit Kumar;Rosaria Medda;Francesca Pintus;Francesco Delogu;Maria J. Matos;Benedetta Era

Penultimate

;Giovanna L. Delogu

Last

2019-01-01

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Abstract

We have designed, synthesized and evaluated a series of hydroxylated 2-phenylbenzofuran derivatives as potential cholinesterase inhibitors. Starting from a series of 2-phenylbenzofurans previously published, in this paper we present a complete synthesis and the influence on the activity of one or two hydroxyl groups located in meta or in meta and para positions respectively of the 2-phenyl ring and highlight the importance of position of hydroxyl groups. Moreover, simultaneous introduction of halogen at position 7 of the benzofuran scaffold resulted in an improved inhibitory activity against the enzyme. To further provide molecular insight and to identify the most probable ligand-binding site of the protein, docking studies were performed for the top-ranked compounds. Docking results revealed conserved ligand-binding residues and supported the role of catalytic site residues in enzyme inhibition.