Synthesis, Enzyme Assays and Molecular Docking Studies of Fluorina ted Bioisosteres of Santacruzamate A as Potential HDAC Tracers

Title:Synthesis, Enzyme Assays and Molecular Docking Studies of Fluorina ted Bioisosteres of Santacruzamate A as Potential HDAC Tracers

Volume: 14 Issue: 7

Author(s): Muneer Ahamed, Koen Vermeulen, Michael Schnekenburger, Lise Roman Moltzau, Finn Olav Levy, Janos Marton, Mathy Froeyen, Dag Erlend Olberg, Marc Diederich and Guy Bormans

Affiliation:

Keywords: HDAC inhibitors, enzyme assays, molecular docking, PET tracers, HDAC, in vitro.

Abstract: Background: Histone deacetylases (HDACs) emerged as important epigenetic regulators of gene expression.

Method: In order to identify potential positron emission tomography (PET) tracers for imaging HDACs, we evaluated in vitro and in cellulo activities of some compounds that were reported as potent HDAC2-selective inhibitors. We observed marked differences between reported activity values and the values obtained in our assays for some of the compounds. To understand the structural basis of the activity of some of these inhibitors, we also performed molecular docking studies to understand their interaction patterns and binding modes with HDAC2.

Results and Conclusion: We observed the low affinity compounds 4, 6 and 7 did not showed equal number of key π-π interactions and hydrogen bonding when compared to high affinity compounds, and could be the possible reason for poor inhibition as reflected in in vitro assays. These preliminary experimental and computational results will help to interpret the HDAC affinity values of these key compounds with caution.

Cite this article as:

Ahamed Muneer, Vermeulen Koen, Schnekenburger Michael, Moltzau Roman Lise, Levy Olav Finn, Marton Janos, Froeyen Mathy, Olberg Erlend Dag, Diederich Marc and Bormans Guy, Synthesis, Enzyme Assays and Molecular Docking Studies of Fluorina ted Bioisosteres of Santacruzamate A as Potential HDAC Tracers, Letters in Drug Design & Discovery 2017; 14 (7) . https://dx.doi.org/10.2174/1570180813666161101152943

DOI https://dx.doi.org/10.2174/1570180813666161101152943	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X