QSAR and Molecular Interaction Study of Piperine Analogues for Antitubercular Activity

In the present work QSAR and molecular docking studies have been performed to explore the binding affinity of 70 novel piperine analogues and 23 reported compounds against Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv). Molecular docking studies for training and test compounds were done against protein Dev R (Uniprot ID: P9WMF8). The DevR-DosR works on two component regulatory system and was concerned in dormancy response of Mycobacterium tuberculosis. The best model from the training set showed r2 value 0.8760 and q2 value 0.7516. The validation of best QSAR model of each series was done by predicting the activity of the test set compounds. We have found that the reported compounds interacted with protein with a range of binding energy from -2.31 k cal/mol to -4.941 kcal/molby formation of one hydrogen bond to four hydrogen bond whereas predicted compounds interacted with binding energy ranges from -2.36 kcal/mol to -5.90kcal/molby forming one hydrogen bond to five hydrogen bonds.Similar pharmacophores containing molecules were designed and their activities were predicted using validated QSAR model and docking scores were also calculated. Some of predicted compounds showed improved binding affinity with the selected protein and some of them showed comparable affinity as compare to reported compounds.