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

Three isolated natural benzofuran compounds 1a-c and four semi-synthesized benzofuran derivatives 2a,b and 3a,b were evaluated for their in vitro 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 1a with IC₅₀ 102.4 ± 5.72 µM. The kellin derivatives 1a, 2a and 3a bearing additional methoxyl group showed more inhibition activity than its analogues of visnagin derivatives 1b,c, 2b and 3b. The in silico investigation on the seven benzofuran derivatives matched our in vitro 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 in silico study showed clearly that compounds carrying additional hydrophobic group had more potent activity through matched more ligand features.