Title

Synthesis and Evaluation of c-Src Kinase Inhibitory Activity of Pyridin-2(1H)-one Derivatives

Authors

Karam Chand
Suchita Prasad
Rakesh K. Tiwari, University of Rhode Island
Amir N. Shirazi, University of Rhode Island
Sumit Kumar
Keykavous Parang, University of Rhode IslandFollow
Sunil K. Sharma

Document Type

Article

Date of Original Version

2014

Department

Biomedical and Pharmaceutical Sciences

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 25 μM. 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 12.5 μM. Further the kinase inhibitory potential of compound 36 was studied for EGFR, MAPK and PDK, however no significant activity was observed at the highest tested concentration (300 μM). These results provide insights for further optimization of this scaffold for designing the next generation of 2-pyridone derivatives as candidate Src kinase inhibitors.

Citation/Publisher Attribution

Chand, K., Prasad, S., Tiwari, R. K., Shirazi, A. N., Kumar, S., Parang, K., & Sharma, S. K. (2014, February 17). Synthesis and evaluation of c-Src kinase inhibitory activity of pyridin-2(1H)-one derivatives. Bioorganic Chemistry, 53, 75-82. doi: 10.1016/j.bioorg.2014.02.001

Available at: http://dx.doi.org/10.1016/j.bioorg.2014.02.001