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Identification of mercaptoacetamide-based HDAC6 inhibitors via a lean inhibitor strategy : screening, synthesis, and biological evaluation

Silke Geurs (UGent) , Dorien Clarisse (UGent) , Freya Baele, Jorick Franceus (UGent) , Tom Desmet (UGent) , Karolien De Bosscher (UGent) and Matthias D'hooghe (UGent)
(2022) CHEMICAL COMMUNICATIONS. 58(42). p.6239-6242
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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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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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