Original Articles
Sanmati K. Jain, Rahul Jain, L
Abstract
Quantitative structure activity relationship (QSAR) study was performed on a series of 3,5-disubstituted-4,5- dihydropyrazole-1-carbothioamides possessing epidermal growth factor receptor (EGFR) kinase inhibitory activity for establishing quantitative relationship between biological activity and their physicochemical / structural properties. Several statistical regression equations were obtained using partial least squares regression (PLSR) analysis. Most statistical significant model generated, explains 77% (r2 = 0.7705) of the total variance in the training set as well as it has internal (q2) and external (pred_r2) predicative ability of ~51% (q2 = 0.5065) and 61% (pred_r2 = 0.6112) respectively. In this model positive coefficient value of T_C_C_4 [This is the count of number of carbon atoms separated from any carbon atom (single, double or triple bonded) by 4 bond distance in a molecule] and SssOcount [ ] on the biological activity indicated that higher value leads to better epidermal growth factor receptor (EGFR) kinase inhibitory activity whereas lower value leads to decrease activity. Negative coefficient value of SKMostHydrophobicHydrophilicDistance [most hydrophobic value on vdW surface] on the biological activity indicated that lower values leads to good epidermal growth factor receptor (EGFR) kinase inhibitory activity while higher value leads to reduced activity. Contribution chart reveals that the descriptors T_C_C_4, SKMostHydrophobicHydrophilicDistance and SssOcount contributing 46.75 %, 32.74% and 20.51% respectively.