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

Karam Chand, Suchita Prasad, Rakesh K. Tiwari, Amir N. Shirazi, Sumit Kumar, Keykavous Parang, Sunil K. Sharma

Research output: Contribution to journalArticle

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 IC 50 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. 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 (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.

Original languageEnglish (US)
Pages (from-to)75-82
Number of pages8
JournalBioorganic Chemistry
Volume53
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

src-Family Kinases
Derivatives
Drug Design
Scaffolds
Inhibitory Concentration 50
Tumors
Phosphotransferases
Pharmaceutical Preparations
CSK tyrosine-protein kinase
Neoplasms
2-hydroxypyridine

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Medicine(all)

Cite this

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

Synthesis and evaluation of c-Src kinase inhibitory activity of pyridin-2(1H)-one derivatives. / Chand, Karam; Prasad, Suchita; Tiwari, Rakesh K.; Shirazi, Amir N.; Kumar, Sumit; Parang, Keykavous; Sharma, Sunil K.

In: Bioorganic Chemistry, Vol. 53, 2014, p. 75-82.

Research output: Contribution to journalArticle

Chand, K, Prasad, S, Tiwari, RK, Shirazi, AN, Kumar, S, Parang, K & Sharma, SK 2014, 'Synthesis and evaluation of c-Src kinase inhibitory activity of pyridin-2(1H)-one derivatives', Bioorganic Chemistry, vol. 53, pp. 75-82. https://doi.org/10.1016/j.bioorg.2014.02.001
Chand, Karam ; Prasad, Suchita ; Tiwari, Rakesh K. ; Shirazi, Amir N. ; Kumar, Sumit ; Parang, Keykavous ; Sharma, Sunil K. / Synthesis and evaluation of c-Src kinase inhibitory activity of pyridin-2(1H)-one derivatives. In: Bioorganic Chemistry. 2014 ; Vol. 53. pp. 75-82.
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AU - Sharma, Sunil K.

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