Isolation, in vitro acetylcholinesterase inhibitory activity, molecular docking, and in silico ADME analysis of compounds from Cadaba farinosa roots

Abstract

Three undescribed compounds were isolated ( 2 , 3 , 5 ) from the roots of Cadaba farinosa Forssk. with twelve known metabolites. In addition, three compounds ( 1 , 4 , 6 ) previously known only from synthetic sources were isolated from the extract and, to our knowledge, have not previously been reported from natural sources. Structural elucidation was performed by comprehensive NMR and HRESI-MS analyses. The anticholinesterase activity of extracts and isolated compounds was assessed in vitro using a modified Ellman’s colorimetric method. Additionally, molecular docking simulations were conducted to predict the binding affinities and interactions of the compounds with the AChE active site. In vitro assays revealed that the p -aminobenzoate derivative ( 1 ) showed the highest AChE inhibition (IC₅₀ = 1.33 ± 0.01 μM). Docking results supported these findings, with 1 suggesting the strongest binding affinity and favorable binding affinity (−4.91 kcal/mol). Compound 1 also displays a more favorable drug-likeness profile, consistent with Lipinski's criteria. These results suggest that C. farinosa contains promising anti-AChE compounds, particularly p -aminobenzoate derivatives, which may serve as lead candidates for the development of new therapies against Alzheimer’s disease.