Synthesis, Biological, and Computational Evaluation of Novel 1,3,5-Substituted Indolin-2-one Derivatives as Inhibitors of Src Tyrosine Kinase

KILIÇ KURT Z., BAKAR ATEŞ F., Olgen S.

ARCHIV DER PHARMAZIE, cilt.348, sa.10, ss.715-729, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 348 Sayı: 10
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1002/ardp.201500109
  • Dergi Adı: ARCHIV DER PHARMAZIE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.715-729
  • Anahtar Kelimeler: Cancer, Indolin-2-one, Molecular docking, Src kinase, Tyrosine kinase activity, C-SRC, ISATIN DERIVATIVES, CELL-LINE, EXPRESSION, CANCER, ACTIVATION, PROTEIN, RECEPTOR, FAMILY, GROWTH
  • Ankara Üniversitesi Adresli: Evet

Özet

Several substituted indolin-2-one derivatives were synthesized and evaluated for their activities against Src kinase. Several compounds showed activity against Src, with IC50 values in the low micromolar range. Among them, compound 2f showed the most significant activity with an IC50 value of 1.02M. Molecular docking studies have been performed for evaluation of the binding modes of compound 2f into the Src active site. The docking structure of compound 2f disclosed that the indole NH forms a hydrogen bond with the carbonyl of Met341. These results suggest that our novel compound 2f is a promising compound for the further development of indole-based drugs targeting Src kinase.