TY - JOUR
T1 - Pro-apoptotic carboxamide analogues of natural fislatifolic acid targeting Mcl-1 and Bcl-2
AU - Gapil Tiamas, Shelly
AU - Daressy, Florian
AU - Abou Samra, Alma
AU - Bignon, Jérome
AU - Steinmetz, Vincent
AU - Litaudon, Marc
AU - Fourneau, Christophe
AU - Hoong Leong, Kok
AU - Ariffin, Azhar
AU - Awang, Khalijah
AU - Desrat, Sandy
AU - Roussi, Fanny
N1 - Funding Information:
This research was conducted within the frame of the International French Malaysian Natural Product Laboratory (IFM-NatProLab) established between CNRS-ICSN and University Malaya. We are grateful to the Bright Spark Unit, University of Malaya, Malaysia and the French Embassy in Malaysia for the scholarship of SGT. We also thank Investissement d'Avenir grant of the Agence Nationale de la Recherche (CEBA: ANR-10-LABX-25-01) for its financial support.
Funding Information:
This research was conducted within the frame of the International French Malaysian Natural Product Laboratory (IFM-NatProLab) established between CNRS-ICSN and University Malaya. We are grateful to the Bright Spark Unit, University of Malaya, Malaysia and the French Embassy in Malaysia for the scholarship of SGT. We also thank Investissement d’Avenir grant of the Agence Nationale de la Recherche (CEBA: ANR-10-LABX-25-01) for its financial support.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/4/1
Y1 - 2020/4/1
N2 - A library of 26 novel carboxamides deriving from natural fislatifolic acid has been prepared. The synthetic strategy involved a bio-inspired Diels-Alder cycloaddition, followed by functionalisations of the carbonyl moiety. All the compounds were evaluated on Bcl-xL, Mcl-1 and Bcl-2 proteins. In this series of cyclohexenyl chalcone analogues, six compounds behaved as dual Bcl-xL/Mcl-1 inhibitors in micromolar range and one exhibited sub-micromolar affinities toward Mcl-1 and Bcl-2. The most potent compounds evaluated on A549 and MCF7 cancer cell lines showed moderate cytotoxicities.
AB - A library of 26 novel carboxamides deriving from natural fislatifolic acid has been prepared. The synthetic strategy involved a bio-inspired Diels-Alder cycloaddition, followed by functionalisations of the carbonyl moiety. All the compounds were evaluated on Bcl-xL, Mcl-1 and Bcl-2 proteins. In this series of cyclohexenyl chalcone analogues, six compounds behaved as dual Bcl-xL/Mcl-1 inhibitors in micromolar range and one exhibited sub-micromolar affinities toward Mcl-1 and Bcl-2. The most potent compounds evaluated on A549 and MCF7 cancer cell lines showed moderate cytotoxicities.
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U2 - 10.1016/j.bmcl.2020.127003
DO - 10.1016/j.bmcl.2020.127003
M3 - Article
C2 - 32035700
AN - SCOPUS:85079049857
SN - 0960-894X
VL - 30
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 7
M1 - 127003
ER -
