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

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dc.authorid0000-0003-0157-2839
dc.authorid0000-0001-5625-0189
dc.authorid0000-0003-0516-6010
dc.authorid0000-0003-3681-9336
dc.authorid0000-0002-5891-7167
dc.authorid0000-0002-9805-2663
dc.authorid0000-0002-7093-4744
dc.authorid0000-0002-8515-8338
dc.authorid0000-0001-8875-3522
dc.authorid0000-0002-1112-5162
dc.authorid0000-0001-7878-9994
dc.contributor.authorCamcı Eren, Merve
dc.contributor.authorCinek, Tuğçe
dc.contributor.authorCihan Üstündağ, Gökçe
dc.contributor.authorÖzen Eroğlu, Güneş
dc.contributor.authorYıldırım, Merve
dc.contributor.authorGenç Akar, Öyküm
dc.contributor.authorErol Bozkurt, Ayşe
dc.contributor.authorSancar, Serap
dc.contributor.authorÖztay, Füsun
dc.contributor.authorSoylu Eter, Özge
dc.contributor.authorBolkent, Şehnaz
dc.contributor.authorKuruca, Serap
dc.date.accessioned2025-02-06T14:20:37Z
dc.date.available2025-02-06T14:20:37Z
dc.date.issued2025
dc.departmentFakülteler, Eczacılık Fakültesi, Eczacılık Meslek Bilimleri Bölümü, Farmasötik Kimya Ana Bilim Dalı
dc.description.abstractIn 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.
dc.identifier.citationCamcı 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
dc.identifier.doi10.1016/j.bioorg.2025.108203
dc.identifier.endpage16
dc.identifier.issn1090-2120
dc.identifier.issn0045-2068
dc.identifier.pmid39864371
dc.identifier.scopus2-s2.0-85215831983
dc.identifier.scopusqualityQ1
dc.identifier.startpage1
dc.identifier.urihttps://doi.org/10.1016/j.bioorg.2025.108203
dc.identifier.urihttps://hdl.handle.net/20.500.13055/910
dc.identifier.volume156
dc.identifier.wosWOS:001413710400001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorCinek, Tuğçe
dc.institutionauthorid0000-0001-5625-0189
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofBioorganic Chemistry
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subject2-Indolinone
dc.subjectAnticancer Activity
dc.subjectTyrosine Kinase
dc.subjectSRC
dc.subjectApoptosis
dc.titleNew 2-indolinone-indole hybrid compounds carrying a benzoyl moiety as tyrosine kinase inhibitors
dc.typeArticle
dspace.entity.typePublication

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