Molecular Docking Studies and Anti-Alzheimer’s Potential of Isolated Compounds from Tinospora cordifolia

Abstract

Inhibition of acetylcholinesterase (AChE) is a promising strategy for the management of Alzheimer’s disease (AD). Prolyl endopeptidase (PEP) is a post-proline cleaving enzyme that plays an important role in learning and memory. This study explore the AChE and PEP inhibitory activities of compounds from T. cordifolia. Their affinity for different binding sites in silico was also evaluated. Ellman’s and β-naphtyl acetate-fast blue salt (NA-FB) assay methods were used to determine the cholinesterase inhibitory activity. PEP inhibition was determined by colorimetric assay according to Yoshimoto. Isolation of bioactive compounds was done by different chromatographic methods and structures established using spectroscopy. Molecular docking was carried out using MOE software suite modeled structures based on the coordinates of PDB ID: 3IVM and 10CE. The ethyl acetate fraction had the best AChE inhibition with an IC50 value of 1.4574 ± 0.47 mg/mL at 5 mg/mL. Nine compounds identified as β-sitosterol, tinosporide, 8-hydroxycolumbin, oxoglaucine, corydine, liriodenine, N-formylanonaine, palmatine, 1-octacosanol were isolated from different fractions with oxoglaucine being reported for the first time in the genus Tinospora. Oxoglaucine, liriodenine and N-formylanonaine demonstrated good AChE inhibitory activity with IC50 values of 0.8033 ± 0.09 mg/mL, 0.8076 ± 0.07 mg/mL and 0.8190 ± 0.06 mg/mL at 1 mg/mL respectively. Oxoglaucine and corydine at 1 mM inhibited prolyl endopeptidase with IC50 values of 0.7802 ± 3.1 mM and 0.7884 ± 3.17 mM respectively. Molecular docking revealed hydrophobic, hydrogen bonding, and Pi-stacking interactions between the ligands and the active site of enzymes. Compounds from Tinospora cordifolia are a possible lead for the development of drugs that may be useful in the management of AD.