Chunqi Hu, Liang Hong, Jun Li and Wenting Du* Pages 798 - 810 ( 13 )
Background: A 3D-QSAR study of histone deacetylase 6 (HDAC6) inhibitors including comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) was carried out.Method: Sixty-six compounds with their in vitro inhibitory activities (IC50 values) were first docked into a homology model of HDAC6 using the LibDock program and then used to generate the training and testing sets of compounds for both the CoMFA and CoMSIA studies. Results and Conclusion: The best CoMFA model produced a q2 of 0.637 and an r2 of 0.987, and the best CoMSIA model produced a q2 of 0.767 and an r2 of 0.987, indicating a high statistical significance as a predictive model. The models and related information may provide important insight into inhibitor–HDAC6 interactions and help in the design of novel potent HDAC inhibitors.
HDAC6 inhibitors, 3D-QSAR, docking-based alignment, CoMFA, CoMSIA, compounds.
Department of Pharmary, Chemistry and Chemical Engineering Institute, Shaoxing University, Shaoxing, 312000, Yongning Pharma, No.4, Meihuajing Road, Huangyan, Taizhou, Zhejiang, 318020, Department of Pharmacy, Hangzhou Medical College, 481 Binwen Road, Hangzhou 310053, Department of Pharmacy, Hangzhou Medical College, 481 Binwen Road, Hangzhou 310053