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Coumarin derivatives as inhibitors of acetylcholinesterase: QSAR study

Coumarin and its derivatives are well-known phytochemicals that have shown great potential in acetylcholinesterase (AChE) inhibition [1]. Novel coumarin derivatives have been tested as acethylcholinesterase (AChE) inhibitors by utilizing the Ellman's method [2]. Inhibition data were expressed as a logarithm of inhibition percentages. Molecular structures were optimized by PM3 method using Hyperchem software. Molecular descriptors have been calculated by ADMEWORKS ModelBuilder software. QSAR analysis for inhibition of AChE was performed on the 34 compounds in the training set. Due to the small number of compounds, they were not split in training and test sets. The best QSAR model obtained is: log inh.% = - 1.09 – 0.11 MATS7m + 1.84 MCB + 0.17 DIPZ (1) where MATS7m is Moran autocorrelation of lag 7, weighted by atomic masses ; MCB is Balabans topological index, and DIPZ is dipole moment on Z axes. The model has achieved the following statistical performance of the internal validation: R2 = 0.78 ; F = 37.26 ; Δk = 0.23 ; CCCtr = 0.88 ; CCCcv = 0.84 ; Q2loo = 0.71 ; Q2γscr = -0.18. Williams plot for applicability domain of model (1) is shown in Figure 1. Molecular descriptors in model (1) revealed that effect of inhibition of molecules decreased with: lower number of atoms higher mass at spatial lag 7, increasing branching, and small difference in electronegativity between two bonded atoms at the Z axes.

Coumarine derivatives ; QSAR ; inhibition

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