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Bioorg Chem. 2014 Apr;53:75-82. doi: 10.1016/j.bioorg.2014.02.001. Epub 2014 Feb 17.

Synthesis and evaluation of c-Src kinase inhibitory activity of pyridin-2(1H)-one derivatives.

Author information

1
Department of Chemistry, University of Delhi, Delhi 110007, India.
2
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The University of Rhode Island, Kingston, RI 02881, USA; School of Pharmacy, Chapman University, One University Drive, Orange, CA 92866, USA.
3
Department of Chemistry, University of Delhi, Delhi 110007, India; Department of Chemistry, Deenbandhu Chhotu Ram University of Science & Technology, Murthal 131039, Haryana, India.
4
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The University of Rhode Island, Kingston, RI 02881, USA; School of Pharmacy, Chapman University, One University Drive, Orange, CA 92866, USA. Electronic address: kparang@uri.edu.
5
Department of Chemistry, University of Delhi, Delhi 110007, India. Electronic address: sk.sharma90@gmail.com.

Abstract

Src kinase, a prototype member of the Src family of kinases (SFKs), is over-expressed in various human tumors, and has become a target for anticancer drug design. In this perspective, a series of eighteen 2-pyridone derivatives were synthesized and evaluated for their c-Src kinase inhibitory activity. Among them, eight compounds exhibited c-Src kinase inhibitory activity with IC50 value of less than 25μM. Compound 1-[2-(dimethylamino)ethyl]-5-(2-hydroxy-4-methoxybenzoyl)pyridin-2(1H)-one (36) exhibited the highest c-Src kinase inhibition with an IC50 value of 12.5μM. Furthermore, the kinase inhibitory activity of compound 36 was studied against EGFR, MAPK and PDK, however no significant activity was observed at the highest tested concentration (300μM). These results provide insights for further optimization of this scaffold for designing the next generation of 2-pyridone derivatives as candidate Src kinase inhibitors.

KEYWORDS:

Chromone; Pyridin-2(1H)-one; Synthesis; c-Src kinase inhibition

PMID:
24632506
DOI:
10.1016/j.bioorg.2014.02.001
[Indexed for MEDLINE]
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