Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 54, Issue 13, Pages 4350-4364Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm2001025
Keywords
-
Categories
Funding
- National Cancer Institute/NIH [R01CA131970]
- INSERM
- University Denis Diderot/Paris 7
- Chaire of Excellence from the Agence Nationale pour la Recherche, France
- NIH [P41 RR-01081, R01 GM070481]
Ask authors/readers for more resources
The design, synthesis, docking, and biological evaluation of novel potent HDAC3 and HDAC8 isoxazole- and pyrazole-based diazide probes suitable for binding ensemble profiling with photoaffinity labeling (BEProFL) experiments in cells is described. Both the isoxazole- and pyrazole-based probes exhibit low nanomolar inhibitory activity against HDAC3 and HDAC8, respectively. The pyrazole-based probe 3f appears to be one of the most active HDAC8 inhibitors reported in the literature with an IC(50) of 17 nM. Our docking studies suggest that unlike the isoxazole-based ligands the pyrazole-based ligands are flexible enough to occupy the second binding site of HDAC8. Probes/inhibitors 2b, 3a, 3c, and 3f exerted the antiproliferative and neuroprotective activities at micromolar concentrations through inhibition of nuclear HDACs, indicating that they are cell permeable and the presence of an azide or a diazide group does not interfere with the neuroprotection properties, or enhance cellular cytotoxicity, or affect cell permeability.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available