Camcı Eren, MerveCinek, TuğçeCihan Üstündağ, GökçeÖzen Eroğlu, GüneşYıldırım, MerveGenç Akar, ÖykümErol Bozkurt, AyşeSancar, SerapÖztay, FüsunSoylu Eter, ÖzgeBolkent, ŞehnazKuruca, Serap2025-02-062025-02-062025Camcı 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.2025.1082031090-21200045-2068https://doi.org/10.1016/j.bioorg.2025.108203https://hdl.handle.net/20.500.13055/910In 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.eninfo:eu-repo/semantics/closedAccess2-IndolinoneAnticancer ActivityTyrosine KinaseSRCApoptosisArticle10.1016/j.bioorg.2025.108203156116Q1WOS:0014137104000012-s2.0-8521583198339864371Q1