PTP1B inhibitors for diabesity: Discovery of new bromophenol derivatives using 3D QSAR and Molecular Docking study

Recent studies have indicated that the bromophenol moiety is essential for Protein tyrosine phosphatase (1B PTP1B) inhibitory activity for the treatment of Diabetes Mellitus (DM). Based on the fact that no PTB1B antagonists have been successfully developed, we attempted to study the relationship of PTP1B inhibition activity and chemical structure in order to ameliorate the potency for PTP1B. The 3D-QSAR method was performed on a series of 20 bromophenol derivatives identified as PTP1B inhibitors using 15 compounds as a training set which showed good statistical quality and a satisfying predictive ability (Q2 = 0.846 and R2=0.952) for CoMFA and (Q2 = 0.808 and R2=0.926) for CoMSIA. A set of five compounds is used as a test set to validate the predictive power of the CoMFA and CoMSIA models which gave an acceptable predictive correlation (rext2) value of 0.802 and 0.787 respectively. The contour maps produced by the CoMFA and CoMSIA models provided insight into the key structural features requirements for the activity. As a result, new selective PTP1B inhibitors are designed and showed higher inhibitory activity than that of the 20 compounds and investigated for its interaction with PTP1Bemploying molecular docking