1. New 2-indolinone-indole hybrid compounds carrying a benzoyl moiety as tyrosine kinase inhibitors.
- Author
-
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, and Karalı N
- Subjects
- Humans, Structure-Activity Relationship, Molecular Structure, Dose-Response Relationship, Drug, Cell Line, Tumor, Molecular Docking Simulation, Protein-Tyrosine Kinases antagonists & inhibitors, Protein-Tyrosine Kinases metabolism, Tyrosine Kinase Inhibitors, Indoles chemistry, Indoles pharmacology, Indoles chemical synthesis, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors chemistry, Protein Kinase Inhibitors chemical synthesis, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents chemical synthesis, Drug Screening Assays, Antitumor, Apoptosis drug effects, Cell Proliferation drug effects
- Abstract
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 IC
50 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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof. Dr. Nilgun Karali reports financial support was provided by Istanbul University Scientific Research Projects Unit. Prof. Dr. Nilgun Karali and Assoc. Prof. Dr. Gokce Cihan Ustundag has patent licensed to TR 2020 050104. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)- Published
- 2025
- Full Text
- View/download PDF