Abstract

 
 
 
 Purpose: To investigate the acetylcholinesterase (AChE) inhibitory potential of columbin and also to assess its binding affinity against AChE protein.
 Methods: Crystals of columbin were isolated from the ethyl acetate fraction of Tinospora cordifolia using column chromatography and its structure was determined using x-ray crystallography. Ellman colorimetric assay was used to determine the AChE inhibitory effect in vitro while molecular docking was performed using the MOE 2015.010 software. The selected protein data bank (PDB) was modeled using PDB ID: 10CE (pacific electric ray).
 Results: The crystal and structure refinement data of columbin were: C20H22O6, Orthorhombic, P212121, a = 7.4951(2) Å (α = 90°), b = 11.6451(3) Å (β = 90°), c = 19.5882(5) Å (γ = 90°), V=1709.68(8) Å3, Z = 4, Density (calculated) = 1.392 Mg/m3, absorption coefficient = 0.851 mm-1, goodness-of-fit on F2 =1.091, T = 100(2) K. Columbin demonstrated good AChE inhibitory effect with half-maximal inhibitory concentration (IC50) of 1.2993 ± 0.17 mg/mL. Molecular docking data revealed that it exhibited hydrophobic and hydrogen bonding interactions with the surrounding residues, and this accelerated complexation between the ligands and the active site of the enzyme.
 Conclusion: Columbin may be useful in the management of neurodegenerative conditions such as Alzheimer’s disease.
 
 
 
Highlights
Molecular docking, a method that helps predict or anticipate the favored orientations of drug candidates against macromolecular targets to make stable complex, has found remarkable importance in drug design and discovery
In patients with a-2-l1-L-;-ic-2-e0--n(-s2--e)-:--3--3-7 disease (AD), there is a drastic decrease in the production and half-life of ACh due to the presence of the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) which catalyzes the breakdown of ACh [5]
The packing arrangement of the molecule showed the presence of five different intermolecular interactions dominant in the crystal structure with no intra-molecular interaction
Summary
A method that helps predict or anticipate the favored orientations of drug candidates (ligands) against macromolecular targets (protein) to make stable complex, has found remarkable importance in drug design and discovery. The present study was aimed at determining the crystal data and structure refinement of columbin isolated from T. cordifolia and assessing its binding affinity against acetylcholinesterase protein. The number of interactions present in the crystal lattices was determined qualitatively and quantitatively via three-dimensional Hirshfeld surface analysis and two-dimensional fingerprint plots, respectively. In order to predict the binding mode of columbin as putative acetylcholinesterase inhibitor [], molecular docking studies were carried out with the available protein data bank (PDB) ID:10CE (acetylcholinesterase (E.C. 3.1.1.7) of the enzyme from Tetronarce californica (Pacific electric ray) complexed with an inhibitor MF268.
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