engleski

Evaluation of the key structural features of various butyrylcholinesterase inhibitors using simple molecular descriptors

In this study we developed several QSAR models based on simple descriptors (like topological and constitutional) to estimate butyrylcholinesterase (BChE) inhibition potency, pKi (or pIC50), of a set of 297 (289 after exclusion of outliers) structurally different compounds. The models were similar to the best model that we obtained previously for acetylcholinesterase AChE and were based on the valence molecular connectivity indices of the second- and third-order (2χv and 3χv), the number of aliphatic hydroxyl groups (nOH), AlogP – Ghose-Crippen octanol-water partition coeff. (logP), and O-060 – atom-centred fragments (Al-O-Ar, Ar-O-Ar, R..O..R, R-O-C=X). The best models with two and three descriptors yielded r = 0.787 and S.E. = 0.89, and r = 0.827 and S.E. = 0.81, respectively. We also correlated nine scoring functions, calculated for 20 ligands whose complexes with BChE we found in the Protein Data Bank as crystal structures, to pKi (or pIC50). The best correlations yielded PLP1 and PLP2 (Piecewise Linear Pairwise potential functions), r = 0.619 and 0.689, respectively. Correlation with certain simple topological and constitutional descriptors yielded better results, e.g. 3χv (r = 0.730), on the same set of compounds (N = 20).

Dementia ; Alzheimer's disease ; Inhibitor ; Butyrylcholinesterase ; QSAR descriptor

nije evidentirano