QSAR analysis of furanone derivatives as potential COX-2 inhibitors : KNN MFA approach

Abstract EN

A series of thirty-two furanone derivatives with their cyclooxygenase-2 inhibitory activity were subjected to quantitative structural-activity relationship analysis to derive a correlation between biological activity as a dependent variable and various descriptors as independent variables by using V-LIFE MDS3.5 software.

The significant 2D QSAR model showed correlation coefficient (r2) = 0.840, standard error of estimation (SEE) = 0.195, and a cross-validated squared correlation coefficient (q2) = 0.773.

The descriptors involved in the building of 2D QSAR model are retention index for six membered rings, total number of oxygen connected with two single bonds, polar surface area excluding P and S plays a significant role in COX-2 inhibition.

3D-QSAR performed via Step Wise K Nearest Neighbor Molecular Field Analysis [(SW) kNN MFA] with partial leastsquare (PLS) technique showed high predictive ability (r2 = 0.7622, q2 = 0.7031 and standard error = 0.3660) explaining the majority of the variance in the data with two principle components.

The results of the present study may be useful in the design of more potent furanone derivatives as COX-2 inhibitors.