Molecular Modeling, Synthesis and Biological Evaluation of N-Phenyl-4-Hydroxy-6-Methyl-2-Quinolone-3-CarboxAmides as Anticancer Agents.

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Dima A SabbahAya M Al-Zuheiri

Abstract

The emergence of phosphatidylinositol 3-kinase (PI3Kα) in cancer development has accentuated its significance as a potential target for anticancer drug design. Twenty one derivatives of N-phenyl-4-hydroxy-6-methyl-2-quinolone-3-carboxamide were synthesized and characterized using NMR (1H and 13C) and HRMS. The derivatives displayed inhibitory activity against human epithelial colorectal adenocarcinoma (Caco-2) and human colon cancer (HCT-116) cell lines: compounds 8 (IC50 Caco-2 = 98 µM, IC50 HCT-116 = 337 µM) and 16 (IC50 Caco-2 = 13 µM, IC50 HCT-116 = 240.2 µM). Results showed that compound 16 significantly affected the gene encoding AKT, BAD, and PI3K. The induced-fit docking (IFD) studies against PI3Kα demonstrated that the scaffold accommodates the kinase domains and forms H-bonds with significant binding residues.

References

Jan 1, 1984·Cancer Metastasis Reviews·M G BrattainB Long
Dec 2, 1999·Experimental Cell Research·B Vanhaesebroeck, M D Waterfield
Jun 1, 2002·Science·Lewis C Cantley
Jul 3, 2002·Nature Reviews. Cancer·Igor Vivanco, Charles L Sawyers
Oct 14, 2003·Drug Discovery Today·Miles CongreveHarren Jhoti
Mar 16, 2004·Science·Yardena SamuelsVictor E Velculescu
Mar 19, 2004·Journal of Medicinal Chemistry·Richard A FriesnerPeter S Shenkin
May 10, 2005·Journal of Combinatorial Chemistry·Gang ChenHualiang Jiang
Jun 14, 2005·Cancer Cell·Yardena SamuelsVictor E Velculescu
Jul 28, 2005·Journal of Chemical Information and Modeling·Suxin ZhengHualiang Jiang
Feb 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Li Zhao, Peter K Vogt
Sep 17, 2008·Oncogene·A Carracedo, P P Pandolfi
Aug 1, 2009·Nature Reviews. Drug Discovery·Pixu LiuJean J Zhao
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Diana MandelkerL Mario Amzel
Apr 10, 2010·Nature Reviews. Molecular Cell Biology·Bart VanhaesebroeckBenoit Bilanges
Sep 28, 2010·Journal of Chemical Information and Modeling·Dima A SabbahHaizhen Zhong
Jan 4, 2012·Bioorganic & Medicinal Chemistry Letters·Dima A SabbahHaizhen Zhong
Nov 20, 2012·Journal of Chemical Information and Modeling·Dima A SabbahHaizhen A Zhong
Jan 24, 2014·Acta Pharmaceutica : a Quarterly Journal of Croatian Pharmaceutical Society and Slovenian Pharmaceutical Society, Dealing with All Branches of Pharmacy and Allied Sciences·Sanaa K BardaweelNour F Almomani
Apr 17, 2016·Bioorganic & Medicinal Chemistry Letters·Kamal SweidanMohammad S Mubarak
Apr 14, 2018·Medicinal Chemistry·Dima A SabbahMohammad S Mubarak

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Citations

Dec 31, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dima A SabbahKamal Sweidan
May 11, 2021·Expert Opinion on Therapeutic Patents·Dima A SabbahHaizhen A Zhong

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Methods Mentioned

BETA
NMR
PCR
X-ray
PCA

Software Mentioned

ChemDraw
MacroModel
alvaDesc
MAESTRO
Kode Cheminformatics
GraphPad Prism
Schrödinger enterprise

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