Publication Type:

Journal Article


BioMed Research International, Hindawi Publishing Corporation, Volume 2014 (2014)



acetylcholinesterase, article, binding site, cholinesterase, cholinesterase inhibitor, conformational transition, correlation coefficient, crystal structure, drug absorption, drug distribution, drug excretion, drug metabolism, hydrogen bond, IC 50, molecular docking, molecular model, pharmacophore, physical chemistry, quantitative structure activity relation, reference database, Virtual reality


In this study, we have employed in silico methodology combining double pharmacophore based screening, molecular docking, and ADME/T filtering to identify dual binding site acetylcholinesterase inhibitors that can preferentially inhibit acetylcholinesterase and simultaneously inhibit the butyrylcholinesterase also but in the lesser extent than acetylcholinesterase. 3D-pharmacophore models of AChE and BuChE enzyme inhibitors have been developed from xanthostigmine derivatives through HypoGen and validated using test set, Fischer's randomization technique. The best acetylcholinesterase and butyrylcholinesterase inhibitors pharmacophore hypotheses Hypo1-A and Hypo1-B, with high correlation coefficient of 0.96 and 0.94, respectively, were used as 3D query for screening the Zinc database. The screened hits were then subjected to the ADME/T and molecular docking study to prioritise the compounds. Finally, 18 compounds were identified as potential leads against AChE enzyme, showing good predicted activities and promising ADME/T properties. © 2014 Shikhar Gupta and C. Gopi Mohan.


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Cite this Research Publication

Swati P. Gupta and Mohan, C. Gb, “Dual binding site and selective acetylcholinesterase inhibitors derived from integrated pharmacophore models and sequential virtual screening”, BioMed Research International, vol. 2014, 2014.