CoMFA and CoMSIA-based designing of resveratrol derivatives as amyloid-beta aggregation inhibitors against Alzheimer's disease

AbstractResveratrol (3,4 ′,5-trihydroxystilbene) has been reported to promote degradation of intracellular amyloid-beta (Aβ) aggregates in Alzheimer’s disease (AD). In the present paper, we report comparative molecular field analysis (CoMFA)-based and comparative molecular similarity indices analysis (CoMSIA)-based thr ee-dimensional quantitative structure–activity relationship (3D-QSAR) study of 30 resveratrol derivatives. The best predictive CoMFA model with correlation coefficients (r2) of 0.905 and 0.908 for training and test sets, respectively, and cross-validated correlation coefficient (q2) of 0.713 was obtained using training and test set of 20 and 10 compounds, respectively. Using the same sets of compounds, the best CoMSIA model exhibiting steric, electrostatic, and hydrophobic fields revealedr2 values of 0.938 and 0.966 for training and test sets, respectively, andq2 value of 0.726. The features obtained from contour maps of both CoMFA and CoMSIA models were used to design a library of hybrid resveratrol derivatives based on a set of six potent A β aggregation inhibitors. The inhibitory potential of the most active compound of this library was found to be close to that of the most active compound of the data set. The results obtained from the present study makes a foundation for the development of effective drugs against Aβ aggregation.

Source: Medicinal Chemistry Research - February 7, 2018 Category: Chemistry Source Type: research