2D-QSAR ANALYSIS OF PHTHALIMIDE DERIVATIVES AS POTENT HYPOGLYCEMIC AGENTSAbstract
A quantitative structure activity relationship study on series of total thirty three pthalimide analogues reported compounds was taken. Pthalimide analogues have several advantages over present ant diabetic drugs. The present drugs target insulin resistance and insulin insufficiency. So, it is believed that agents will be available alternative to other second line treatment options including sulfonylurea TZDs, DPP-4 inhibitors. Several statistical regression expressions were obtained using stepwise multiple linear regression analysis (MLR) and partial least square analysis (PLS). Pthalimide analogues activity is described by models that are built on simple 2D molecular descriptors and nevertheless are of good quality and predictive power. The results obtained after performing QSAR were; r2 = 0.8986, (MLR method) (equation-1), (equation-2) r2 = 0.6898 (PLS method) The parameters that are found to have significant correlation with hypoglycemic activity are Hosoya Index which is signifies the topological index or Z index, negatively contributing in the biological activity (~40%). The next descriptor is T_N_N_4 i.e. number of Nitrogen atoms (single double or triple bonded) separated from any other Nitrogen atom (single double or triple bonded) by 4 bonds in a molecule. is inversely proportional to the activity (~30%) which mainly indicates the relationship with reference to distance between two nitrogen atoms. The descriptor XK Average Hydrophilicity i.e. Average hydrophilic value also negatively. The r2 and r (CV) 2 values of PCR and PLS models clearly indicate the predictive ability of these models.
Sumitra Nain*, Garima Mathur and Anu Sharma
Department of Pharmacy, Banasthali University, Banasthali, Rajasthan, India
24 June, 2013
12 August, 2013
17 October, 2013
01 November, 2013