2. Academic Validation
  3. New 2-indolinone-indole hybrid compounds carrying a benzoyl moiety as tyrosine kinase inhibitors

New 2-indolinone-indole hybrid compounds carrying a benzoyl moiety as tyrosine kinase inhibitors

  • Bioorg Chem. 2025 Mar:156:108203. doi: 10.1016/j.bioorg.2025.108203.
Merve Camcı-Eren 1,  Tuğçe Cinek 2,  Gökçe Cihan-Üstündağ 3,  Güneş Özen-Eroğlu 4,  Merve Yıldırım 5,  Öyküm Genç-Akar 5,  Ayşe Erol-Bozkurt 6,  Serap Sancar 5,  Füsun Öztay 5,  Özge Soylu-Eter 7,  Şehnaz Bolkent 5,  Serap Kuruca 8,  Nilgün Karalı 3
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Istanbul University 34116 Istanbul, Turkey. Electronic address: mervecamci@istanbul.edu.tr.
  • 2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Istanbul Health and Technology University 34275 Istanbul, Turkey; Health Sciences Institute, Istanbul University 34126 Istanbul, Turkey.
  • 3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Istanbul University 34116 Istanbul, Turkey.
  • 4 Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine 34093 Istanbul, Turkey.
  • 5 Department of Biology, Faculty of Science, Istanbul University 34134 Istanbul, Turkey.
  • 6 Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University 34093 Istanbul, Turkey.
  • 7 Department of Pharmaceutical Technology, Faculty of Pharmacy, Fırat University 23119 Elazığ, Turkey.
  • 8 Department of Physiology, Faculty of Medicine, Istanbul Atlas University 34408 Istanbul, Turkey.
PMID: 39864371 DOI: 10.1016/j.bioorg.2025.108203
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 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.

Keywords

2-indolinone; Anticancer activity; Apoptosis; SRC; Tyrosine kinase.

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