Exploring QSAR on 3-aminopyrazoles as antitumor agents for their inhibitory activity of CDK2/cyclin A

Chemical inhibitors of cyclin-dependent kinases have great therapeutic potential against various proliferative and neurodegenerative disorders. The pharmacophoric requirement of 3-aminopyrazole, inhibitors of CDK2/cyclin A as antitumor agents was explored. QSAR study was performed using ETSA index, RTSA index, indicator parameters and atomic charges to consider quantitatively the effect of the structural variation on the antitumor activity of 3-aminopyrazole. Result showed that atom number 5 is important for the activity. It plays some electronic roles in the interaction of these compounds with enzymes as well as assumed to be involved through the dispersive/van der Waals interactions with enzyme. Presence of meta substitutions on the phenyl ring indicate the detrimental effects towards the activity. The presence of substituted biphenyl/2-thenyl phenyl at R1 are favorable towards the activity. QSAR study also indicates that with increasing the electronegativity of oxygen at position 8, the activity increases.

QSAR study was performed using atom level topological descriptors like ETSA indices, RTSA indices as well as indicator parameters and atomic charges (partial charge) to consider quantitatively the effect of the structural variation on the antitumor activity of 3-aminopyrazole, inhibitors of CDK2/cyclin A.Figure optionsDownload as PowerPoint slide