Development and Validation of a Robust QSAR Model For Piperazine and Keto Piperazine Derivatives as Renin Inhibitors
Jimish R. Patel, Laxman M. Prajapati · Open Pharmaceutical Sciences Journal · 2016
Background:The renin is a key performer in the renin-angiotensin system, and it offers a resource for the beneficial action of hypertension and heart malfunction.The keto piperazine based renin inhibitors have shown greater potential and good biavaibility. Objective:To develop a highly efficient QSAR model for 80 piperazines and keto piperazines to predict renin enzyme inhibitory activity. Methods:The renin inhibitory activity (IC 50 ) was considered as biological activity.Dragon software, version 5.5 was used for calculation of physicochemical parameters.Sequential MLR (multiple linear regression) is carried out to create quantitative structure-activity relationship models, which were again evaluated in support of statistical significance and analytical capacity by inner and exterior validation. Results:The greatest QSAR model was a correlation coefficient (R 2 ) of 0.846, cross-validation correlation coefficient (Q 2 ) of 0.818 and, R 2 pred of 0.821.The leave one out cross validation method was used to assess the performance of the chosen model. Conclusion:The quantitative structure-activity relationship model suggests that the constitutional descriptors (Sv, nDB, nO) play a vital role in binding of ligands with renin enzyme.The information presented provides important structural insight in designing more potent renin enzyme inhibitors.