Babitha Pallikkara Pulikkal, Sahila Mohammed Marunnan, Srinivas Bandaru, Mukesh Yadav, Anuraj Nayarisseri* and Sivanpillai Sureshkumar* Pages 1093 - 1099 ( 7 )
Background: Deficits in cholinergic neurotransmission due to the degeneration of cholinergic neurons in the brain are believed to be one of the major causes of the memory impairments associated with AD. Targeting acetyl cholinesterase (AChE) surfaced as a potential therapeutic target in the treatment of Alzheimer's disease. The present study is pursued to develop quantitative structure activity relationship (QSAR) models to determine chemical descriptors responsible for AChE activity.
Methods: Two different sets of AChE inhibitors, dataset-I (30 compounds) and dataset-II (20 compounds) were investigated through MLR aided linear and SVM aided non-linear QSAR models.
Results: The obtained QSAR models were found statistically fit, stable and predictive on validation scales. These QSAR models were further investigated for their common structure-activity relationship in terms of overlapping molecular descriptors selection. Atomic mass weighted 3D Morse descriptors (MATS5m) and Radial Distribution Function (RDF045m) descriptors were found in common SAR for both the datasets. Electronegativity weighted (MATS5e, HATSe, and Mor17e) descriptors have also been identified in regulative roles towards endpoint values of dataset-I and dataset-II.
Conclusion: The common SAR identified in these linear and non-linear QSAR models could be utilized to design novel inhibitors of AChE with improved biological activity.
Alzheimer's disease, AChE inhibitors, linear and non-linear QSAR models, descriptors sensitivity, SAR.
Research and Development Center, Bharathiyar University, Coimbatore-641046, Tamilnadu, Department of Bioinformatics, School of Life Sciences, Karpagam University, Coimbatore-641021, Bioinformatics Research Laboratory, Eminent Biosciences, Vijaynagar, Indore-452010, Bioinformatics Research Laboratory, Eminent Biosciences, Vijaynagar, Indore-452010, Bioinformatics Research Laboratory, Eminent Biosciences, Vijaynagar, Indore-452010, School of Ocean Science and Technology, Kerala University of Fisheries and Ocean Studies, Panangad-682 506, Cochin