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.
TY - 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 - http://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",
url = "http://farfar.pharmacy.bg.ac.rs/handle/123456789/3354",
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"
}
