New 2-indolinone-indole hybrid compounds carrying a benzoyl moiety as tyrosine kinase inhibitors
Yükleniyor...
Dosyalar
Tarih
2025
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
In this study, new 2-indolinone-indole hybrid compounds (4a-s) carrying a benzoyl moiety were synthesized and their cytotoxic effects were examined against pancreatic (MIA-PaCa-2) and colon (HT-29 and HCT-116) cancer cells by MTT assays. Most of the tested compounds exhibited a better inhibitory activity and safety profile than the reference standard sunitinib malate against MIA-PaCa-2 and HCT-116 cancer cells. Compound 4e displayed the greatest cytotoxic effect on HCT-116 cell with an IC50 value of 0.16 µM and a remarkable selectivity profile (SI > 625). Compound 4g exhibited a selective activity against HCT-116 cancer cell (IC50 = 0.34 µM), with no activity against the other cells at the highest concentrations tested. Compound 4b demonstrated a potent inhibitory activity against MIA-PaCa-2 cell (IC50 = 0.54 µM). General tyrosine kinase inhibitor (TKI) activities and apoptotic effects were examined for compounds 4b, 4e and 4g. The tested compounds were observed to significantly reduce general TK activities in HCT-116 cell and induce apoptosis in HCT-116 and MIA-PaCa-2 cells. Lead compound 4e, the most effective general TKI, was determined to have a specific SRC kinase inhibitor effect in HCT-116 cell and the molecular modelling studies were performed to understand the potential binding mode at the ATP-binding domain of SRC kinase.
Açıklama
Anahtar Kelimeler
2-Indolinone, Anticancer Activity, Tyrosine Kinase, SRC, Apoptosis
Kaynak
Bioorganic Chemistry
WoS Q Değeri
Q1
Scopus Q Değeri
Q1
Cilt
156
Sayı
Künye
Camcı Eren, M., Cinek, T., Cihan Üstündağ, G., Özen Eroğlu, G., Yıldırım, M., Genç Akar, Ö., Erol Bozkurt, A., Sancar, S., Öztay, F., Soylu Eter, Ö., Bolkent, Ş., Kuruca, S., & Karalı, Nilgün. (2025). New 2-indolinone-indole hybrid compounds carrying a benzoyl moiety as tyrosine kinase inhibitors. Bioorganic Chemistry, 156, pp. 1-16. https://doi.org/10.1016/j.bioorg.2025.108203
