Extending Cross Metathesis To Identify Selective HDAC Inhibitors: Synthesis, Biological Activities, and Modeling
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2019
Authors
Bouchet, SamuelLinot, Camille
Ružić, Dušan
Agbaba, Danica
Fouchaq, Benoit
Roche, Joelle
Nikolić, Katarina
Blanquart, Christophe
Bertrand, Philippe
Article (Published version)
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Dissymmetric cross metathesis of alkenes as a convergent and general synthetic strategy allowed for the preparation of a new small series of human histone deacetylases (HDAC) inhibitors. Alkenes bearing Bocprotected hydroxamic acid and benzamide and trityl-protected thiols were used to provide the zinc binding groups and were reacted with alkenes bearing aromatic cap groups. One compound was identified as a selective HDAC6 inhibitor lead. Additional biological evaluation in cancer cell lines demonstrated its ability to stimulate the expression of the epithelial marker E-cadherin and tumor suppressor genes like SEMA3F and p21, suggesting a potential use of this compound for lung cancer treatment. Molecular docking on all 11 HDAC isoforms was used to rationalize the observed biological results.
Keywords:
Cross metathesis / histone deacetylases / lung cancer / epigenetics / molecular modelingSource:
ACS Medicinal Chemistry Letters, 2019, 10, 6, 863-868Publisher:
- Amer Chemical Soc, Washington
Funding / projects:
DOI: 10.1021/acsmedchemlett.8b00440
ISSN: 1948-5875
PubMed: 31223439
WoS: 000471834600006
Scopus: 2-s2.0-85066886661
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PharmacyTY - JOUR AU - Bouchet, Samuel AU - Linot, Camille AU - Ružić, Dušan AU - Agbaba, Danica AU - Fouchaq, Benoit AU - Roche, Joelle AU - Nikolić, Katarina AU - Blanquart, Christophe AU - Bertrand, Philippe PY - 2019 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3354 AB - Dissymmetric cross metathesis of alkenes as a convergent and general synthetic strategy allowed for the preparation of a new small series of human histone deacetylases (HDAC) inhibitors. Alkenes bearing Bocprotected hydroxamic acid and benzamide and trityl-protected thiols were used to provide the zinc binding groups and were reacted with alkenes bearing aromatic cap groups. One compound was identified as a selective HDAC6 inhibitor lead. Additional biological evaluation in cancer cell lines demonstrated its ability to stimulate the expression of the epithelial marker E-cadherin and tumor suppressor genes like SEMA3F and p21, suggesting a potential use of this compound for lung cancer treatment. Molecular docking on all 11 HDAC isoforms was used to rationalize the observed biological results. PB - Amer Chemical Soc, Washington T2 - ACS Medicinal Chemistry Letters T1 - Extending Cross Metathesis To Identify Selective HDAC Inhibitors: Synthesis, Biological Activities, and Modeling VL - 10 IS - 6 SP - 863 EP - 868 DO - 10.1021/acsmedchemlett.8b00440 ER -
@article{ author = "Bouchet, Samuel and Linot, Camille and Ružić, Dušan and Agbaba, Danica and Fouchaq, Benoit and Roche, Joelle and Nikolić, Katarina and Blanquart, Christophe and Bertrand, Philippe", year = "2019", abstract = "Dissymmetric cross metathesis of alkenes as a convergent and general synthetic strategy allowed for the preparation of a new small series of human histone deacetylases (HDAC) inhibitors. Alkenes bearing Bocprotected hydroxamic acid and benzamide and trityl-protected thiols were used to provide the zinc binding groups and were reacted with alkenes bearing aromatic cap groups. One compound was identified as a selective HDAC6 inhibitor lead. Additional biological evaluation in cancer cell lines demonstrated its ability to stimulate the expression of the epithelial marker E-cadherin and tumor suppressor genes like SEMA3F and p21, suggesting a potential use of this compound for lung cancer treatment. Molecular docking on all 11 HDAC isoforms was used to rationalize the observed biological results.", publisher = "Amer Chemical Soc, Washington", journal = "ACS Medicinal Chemistry Letters", title = "Extending Cross Metathesis To Identify Selective HDAC Inhibitors: Synthesis, Biological Activities, and Modeling", volume = "10", number = "6", pages = "863-868", doi = "10.1021/acsmedchemlett.8b00440" }
Bouchet, S., Linot, C., Ružić, D., Agbaba, D., Fouchaq, B., Roche, J., Nikolić, K., Blanquart, C.,& Bertrand, P.. (2019). Extending Cross Metathesis To Identify Selective HDAC Inhibitors: Synthesis, Biological Activities, and Modeling. in ACS Medicinal Chemistry Letters Amer Chemical Soc, Washington., 10(6), 863-868. https://doi.org/10.1021/acsmedchemlett.8b00440
Bouchet S, Linot C, Ružić D, Agbaba D, Fouchaq B, Roche J, Nikolić K, Blanquart C, Bertrand P. Extending Cross Metathesis To Identify Selective HDAC Inhibitors: Synthesis, Biological Activities, and Modeling. in ACS Medicinal Chemistry Letters. 2019;10(6):863-868. doi:10.1021/acsmedchemlett.8b00440 .
Bouchet, Samuel, Linot, Camille, Ružić, Dušan, Agbaba, Danica, Fouchaq, Benoit, Roche, Joelle, Nikolić, Katarina, Blanquart, Christophe, Bertrand, Philippe, "Extending Cross Metathesis To Identify Selective HDAC Inhibitors: Synthesis, Biological Activities, and Modeling" in ACS Medicinal Chemistry Letters, 10, no. 6 (2019):863-868, https://doi.org/10.1021/acsmedchemlett.8b00440 . .