Identification of mercaptoacetamide-based HDAC6 inhibitors via a lean inhibitor strategy : screening, synthesis, and biological evaluation
- Author
- Silke Geurs (UGent) , Dorien Clarisse (UGent) , Freya Baele, Jorick Franceus (UGent) , Tom Desmet (UGent) , Karolien De Bosscher (UGent) and Matthias D'hooghe (UGent)
- Organization
- Abstract
- Non-selective inhibition of different histone deacetylase enzymes by hydroxamic acid-based drugs causes severe side effects when used as a (long-term) cancer treatment. In this work, we searched for a potent zinc-binding group able to replace the contested hydroxamic acid by employing a lean inhibitor strategy. This instructed the synthesis of a set of HDAC6-selective inhibitors containing the more desirable mercaptoacetamide moiety. Biological evaluation of these new compounds showed an IC50 in the nanomolar range, dose-dependent HDAC6 inhibition in MM1.S cells and improved genotoxicity results, rendering these new inhibitors valuable hits for applications even beyond oncology.
- Keywords
- DEACETYLASE 6 HDAC6, HISTONE DEACETYLASES, POTENT, DESIGN, ACETYLATION, ANALOGS, CANCER, ACIDS
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8752799
- MLA
- Geurs, Silke, et al. “Identification of Mercaptoacetamide-Based HDAC6 Inhibitors via a Lean Inhibitor Strategy : Screening, Synthesis, and Biological Evaluation.” CHEMICAL COMMUNICATIONS, vol. 58, no. 42, 2022, pp. 6239–42, doi:10.1039/d2cc01550a.
- APA
- Geurs, S., Clarisse, D., Baele, F., Franceus, J., Desmet, T., De Bosscher, K., & D’hooghe, M. (2022). Identification of mercaptoacetamide-based HDAC6 inhibitors via a lean inhibitor strategy : screening, synthesis, and biological evaluation. CHEMICAL COMMUNICATIONS, 58(42), 6239–6242. https://doi.org/10.1039/d2cc01550a
- Chicago author-date
- Geurs, Silke, Dorien Clarisse, Freya Baele, Jorick Franceus, Tom Desmet, Karolien De Bosscher, and Matthias D’hooghe. 2022. “Identification of Mercaptoacetamide-Based HDAC6 Inhibitors via a Lean Inhibitor Strategy : Screening, Synthesis, and Biological Evaluation.” CHEMICAL COMMUNICATIONS 58 (42): 6239–42. https://doi.org/10.1039/d2cc01550a.
- Chicago author-date (all authors)
- Geurs, Silke, Dorien Clarisse, Freya Baele, Jorick Franceus, Tom Desmet, Karolien De Bosscher, and Matthias D’hooghe. 2022. “Identification of Mercaptoacetamide-Based HDAC6 Inhibitors via a Lean Inhibitor Strategy : Screening, Synthesis, and Biological Evaluation.” CHEMICAL COMMUNICATIONS 58 (42): 6239–6242. doi:10.1039/d2cc01550a.
- Vancouver
- 1.Geurs S, Clarisse D, Baele F, Franceus J, Desmet T, De Bosscher K, et al. Identification of mercaptoacetamide-based HDAC6 inhibitors via a lean inhibitor strategy : screening, synthesis, and biological evaluation. CHEMICAL COMMUNICATIONS. 2022;58(42):6239–42.
- IEEE
- [1]S. Geurs et al., “Identification of mercaptoacetamide-based HDAC6 inhibitors via a lean inhibitor strategy : screening, synthesis, and biological evaluation,” CHEMICAL COMMUNICATIONS, vol. 58, no. 42, pp. 6239–6242, 2022.
@article{8752799, abstract = {{Non-selective inhibition of different histone deacetylase enzymes by hydroxamic acid-based drugs causes severe side effects when used as a (long-term) cancer treatment. In this work, we searched for a potent zinc-binding group able to replace the contested hydroxamic acid by employing a lean inhibitor strategy. This instructed the synthesis of a set of HDAC6-selective inhibitors containing the more desirable mercaptoacetamide moiety. Biological evaluation of these new compounds showed an IC50 in the nanomolar range, dose-dependent HDAC6 inhibition in MM1.S cells and improved genotoxicity results, rendering these new inhibitors valuable hits for applications even beyond oncology.}}, author = {{Geurs, Silke and Clarisse, Dorien and Baele, Freya and Franceus, Jorick and Desmet, Tom and De Bosscher, Karolien and D'hooghe, Matthias}}, issn = {{1359-7345}}, journal = {{CHEMICAL COMMUNICATIONS}}, keywords = {{DEACETYLASE 6 HDAC6,HISTONE DEACETYLASES,POTENT,DESIGN,ACETYLATION,ANALOGS,CANCER,ACIDS}}, language = {{eng}}, number = {{42}}, pages = {{6239--6242}}, title = {{Identification of mercaptoacetamide-based HDAC6 inhibitors via a lean inhibitor strategy : screening, synthesis, and biological evaluation}}, url = {{http://doi.org/10.1039/d2cc01550a}}, volume = {{58}}, year = {{2022}}, }
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