In silico screening for identification of pyrrolidine derivatives dipeptidyl peptidase-IV inhibitors using COMFA, CoMSIA, HQSAR and docking studies.

To explore the relationship between the structures of substituted pyrrolidine derivatives and their inhibition of dipeptidyl peptidase IV inhibitors. The QSAR, including CoMFA, CoMSIA and HQSAR, were applied to identify the key structures impacting their inhibitory potencies. The CoMFA, CoMSIA and HQSAR with cross-validated correlation coefficient (q2 ) value of 0.727, 0.870 and 0.939 and r2 value of 0.973, 0.981 and 0.949. Based on the structure-activity relationship revealed by the present study, we have designed a set of novel dipeptidyl peptidase IV inhibitors that showed excellent potencies in the developed models. Thus, our results allowed us to design new derivatives with desired activities.