Natural benzofuran derivatives as promising scaffold for alleviating Alzheimer symptoms: acetylcholinesterase inhibition, structure activity relationship and <i>in silico</i> studies

Three isolated natural benzofuran compounds <b>1a-c</b> and four semi-synthesized benzofuran derivatives <b>2a,b</b> and <b>3a,b</b> were evaluated for their <i>in vitro</i> acetylcholinesterase inhibition assay. Most of the tested compounds showed moderate activity with IC₅₀ ranged from 102.4 ± 5.72 µM to 565.75 ± 4.17 µM, the most potent compound was kellin <b>1a</b> with IC₅₀ 102.4 ± 5.72 µM. The kellin derivatives <b>1a, 2a</b> and <b>3a</b> bearing additional methoxyl group showed more inhibition activity than its analogues of visnagin derivatives <b>1b,c</b>, <b>2b</b> and <b>3b</b>. The <i>in silico</i> investigation on the seven benzofuran derivatives matched our <i>in vitro</i> acetylcholinesterase results and explains the similarity in structures between the benzofuran compounds and donepezil drug. khellin had the best pharmacophore features among the studied compounds, the best fit score 1.862 and best dock score −9.135. In addition, our <i>in silico</i> study showed clearly that compounds carrying additional hydrophobic group had more potent activity through matched more ligand features.