Stereochemical investigations of bioactive dihydrobenzofuran-type lignanamides from Solanum lyratum: chiral resolution, in vitro and in silico profiling

Abstract

Six pairs of enantiomeric dihydrobenzofuran-type lignanamides consisting of nine undescribed compounds (1a, 2a/2b–3a, and 4b–6a/6b), along with a previously undescribed racemic mixture (7), were isolated from Solanum lyratum (Solanaceae), and the separations of the enantiomers were accomplished by chiral-phase HPLC. The structures of these undescribed compounds were elucidated via analysis of spectroscopic data, and a Rh₂(OCOCF₃)₄-induced circular dichroism (ICD) method. All isolated compounds were assessed for neuroprotective activities in H₂O₂-induced human neuroblastoma SH-SY5Y cells, and acetylcholinesterase (AChE) inhibitory activities. Among the tested isolates, 3b exhibited significant neuroprotective activity at 25 and 50 μmol L⁻¹, 2b, 4a, 6a, and 6b exhibited moderate neuroprotective effects at 12.5, 25, and 50 μmol L⁻¹, and 2a and 6a exerted relatively better AChE inhibitory activity. The molecular docking studies were successfully performed to illustrate the binding between compound 2a and the active sites of AChE.