About Authors:
Dr. A. K. Pathak, Parul Sengar, Kamlesh Kumar*
Department of Pharmacy, Barkatullah University
Bhopal, M. P.
Abstract
A Quantitative Structure Activity Relationship study on a Series of 40 molecules of (4-Quinolylhydrazone compounds) with anti-tubercular activity analogues was made using combination of various physicochemical descriptors (Thermodynamic, electronic and spatial). Several statistical expressions for 2D QSAR & 3D QSAR were developed using stepwise partial least square (PLS) regression analysis and K-Nearest neighboring molecular field analysis (K-NNMFA) respectively. The studies on 2D-QSAR, suggested the four descriptors T_C_C_2, T_C_N_4, Surface area excluding P & S, SsCH3E-index, and H donor count were common and highly contributed the activity. 2DQSAR model developed using partial least square regression approach. Negative logarithmic value of (MIC) was taken as dependent variable and selected discriptors were taken as independent varable. The analysis resulted in the following 2D-equation suggest that, MIC50 = [+0.1587 T_C_C_2- 0.0593 SsCH3E-index- 0.1395 T_C_N_4+ 0.3888 H-Donor Count -3.1556], n =26; Degree of freedom = 22; r2 = 0.75; q2 = 0.67; F test = 22.63; r2 se = 0.20 ; q2 se = 0.23; pred_r2 = 0.46 ; pred_r2 se = 0.24, a H-donor group at Ar, is important for guiding the design of a new molecule. 3DQSAR model developed using K-nearest neighbour method (training set =33 and test set = 7). The best model derived by the method have q2 = 0.51, q2_se = 0.25, Predr2 = 0.71, pred_r2se = 0.16, n=33, k Nearest Neighbor is 2, Degree of freedom =28. The steric and electrostatic descriptors at the grid points, E_916 (0.1865, 0.3006); S_591 (-0.2851, -0.2580); S_1027 (-0.3273, -0.3090); S926 (30.000, 30.000) plays important role for design of new molecule. 3DQSAR analysis of series of 4-Quinolylhydrazone compounds informed that electropositive and less bulky group increases the biological activity.
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