Synthesis and biological study of novel indole-3-imine-2-on derivatives as src kinase and glutathione S-transferase inhibitors

KILIÇ KURT Z., AYDIN D., İŞGÖR Y. G., Işgör B., Olgen S.

Letters in Drug Design and Discovery, cilt.10, sa.1, ss.19-26, 2013 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 10 Sayı: 1
  • Basım Tarihi: 2013
  • Doi Numarası: 10.2174/157018013804142456
  • Dergi Adı: Letters in Drug Design and Discovery
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.19-26
  • Anahtar Kelimeler: Cancer, Drug resistance, Glutathion-S-transferase, Isatine, Src tyrosine kinase, Synthesis
  • Ankara Üniversitesi Adresli: Evet

Özet

The aim of this study is to design and synthesize novel dual inhibitors of Src protein tyrosine kinase (PTK) and Glutathione S-transferases (GSTs), as a potential drug lead with therapeutic efficacy on cancer and immune disorders. The biological activity profiling of small molecule inhibitors via miniaturized biochemical techniques compatible with medium throughput screening and focused screening methodologies were performed. To determining the effects of small molecule inhibitors on Src kinase and Phase II detoxification enzyme GST isozymes in liver homogenates used to verify their roles in drug resistance mechanism for cancer chemotherapeutics. In this study, 14 indole-3-imine-2-on and N-benzyl indole-3-imine-2-on derivatives were synthesized for dual activities against Src and GST. The chemical structures and purities of compounds were verified by IR, 1H NMR, MASS spectroscopy, and elemental analysis. The compounds 2, 3 and 9 are found slightly active against both enzyme Src and GST. © 2013 Bentham Science Publishers.