3D-QSAR Studies of HDAC6 Inhibitors Using Docking-Based Alignment

Author(s): Chunqi Hu, Liang Hong, Jun Li, Wenting Du*.

Journal Name: Letters in Drug Design & Discovery

Volume 14 , Issue 7 , 2017

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Abstract:

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.

Keywords: HDAC6 inhibitors, 3D-QSAR, docking-based alignment, CoMFA, CoMSIA, compounds.

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Article Details

VOLUME: 14
ISSUE: 7
Year: 2017
Page: [798 - 810]
Pages: 13
DOI: 10.2174/1570180813666161028165151
Price: $58

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