COMPARATIVE MOLECULAR FIELD (CoMFA) STUDIES ON [1,2,4] TRIAZOLO [1,5-a] PYRIMIDINES, A CLASS OF ANTICANCER AGENTS, INHIBITION OF TUBULIN

摘要

3D quantitive-structure-activity relationship (3D-QSAR ) analyses were carried out on [1,2,4] triazolo [1,5-a] pyrimidines, a class of anticancer agents. This study correlates the tubulin inhibitory activity of 35 structurally related [1,2,4] triazolo [1,5-a] pyrimidines derived to parabolic region in advanced CoMFA. The CoMFA model using the data on base alignment conformation gave good internal prediction and their cross-validated r~2 values are 0.459 in parabolic region and parabolic region with focus 0.759. The contour maps obtained from 3D-QSAR studies were appraised for the activity trends of the molecules analysed. The results indicate that the steric and electrostatic substitution play significant role in tubulin inhibition activity and potency of these compounds. The data generated from the present study can be used as putative pharmacophore in the design of novel, potent, anticancer agent with tubulin inhibition.