Mtor pathway inhibition, anticancer activity and in silico calculations of novel hydrazone derivatives in two- and three-dimensional cultured type 1 endometrial cancer cells

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dc.contributor.authorBülbül, Muhammet Volkan
dc.contributor.authorMermer, Arif
dc.contributor.authorKolbaşı, Bircan
dc.contributor.authorKocabaş, Fatih
dc.contributor.authorKalender, Semiha Mervenur
dc.contributor.authorKireçtepe Aydın, Kıymet Aslı
dc.contributor.authorKeskin, İlknur
dc.date.accessioned2026-01-06T17:14:14Z
dc.date.available2026-01-06T17:14:14Z
dc.date.issued2024
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Histoloji ve Embriyoloji Ana Bilim Dalı
dc.description.abstractBackground: Endometrial cancer remains a significant health concern, with type 1 endometrial cancer characterized by aberrant expression of estrogen-dependent and mTOR pathway proteins. In this study, we evaluated the effects of two novel hydrazone derivatives against the Ishikawa cell line, a model for endometrial cancer. Methods: Two novel hydrazone derivatives, MVB1 and MVB2, were synthesized and characterized. The anticancer activity of the compounds in both two- and three-dimensional cultured Ishikawa cells was evaluated by MTT assay. The interaction of the compounds with proteins in the PI3K/AKT/mTOR pathway was evaluated by molecular docking studies and in vitro western blot analyses were performed. Additionally, ADME/T calculations were performed to evaluate the drug-like properties of the compounds. Results: MVB1 and MVB2 showed promising anticancer activity with IC50 values of 8.3 ± 0.5 µM and 9.0 ± 1.2 µM in 2D cultures, respectively, and 49.9 ± 2 µM and 20.6 ± 1.9 µM in 3D cultures, respectively. Molecular docking studies revealed significant interactions between these compounds and key proteins in the PI3K/AKT/mTOR pathway, with MVB1 exhibiting the highest mean binding score (−10.5 kcal/mol) among PI3K, AKT1, and mTOR proteins. In vitro studies confirmed that MVB1 effectively suppressed PI3K protein expression in both 2D and 3D cultures (p ≤ 0.0001). Conclusions: The findings suggest that MVB1 and MVB2, especially MVB1, are promising candidates for further development as potential therapeutics for endometrial cancer by targeting the PI3K/AKT/mTOR pathway.
dc.identifier.citationBülbül, M. V., Mermer, A., Kolbaşı, B., Kocabaş, F., Kalender, S. M., Kireçtepe Aydın, K. A. ... Keskin, İ. (2024). Mtor pathway inhibition, anticancer activity and in silico calculations of novel hydrazone derivatives in two- and three-dimensional cultured type 1 endometrial cancer cells. Pharmaceuticals, 17(12). http://dx.doi.org/10.3390/ph17121562
dc.identifier.doi10.3390/ph17121562
dc.identifier.issn1424-8247
dc.identifier.issue12
dc.identifier.pmid39770404
dc.identifier.scopus2-s2.0-85213245288
dc.identifier.scopusqualityQ1
dc.identifier.urihttp://dx.doi.org/10.3390/ph17121562
dc.identifier.urihttps://hdl.handle.net/20.500.12511/13354
dc.identifier.volume17
dc.identifier.wosWOS:001383935600001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorKolbaşı, Bircan
dc.institutionauthorKalender, Semiha Mervenur
dc.institutionauthorKeskin, İlknur
dc.institutionauthorid0000-0001-7933-4262
dc.institutionauthorid0000-0002-0885-3417
dc.institutionauthorid0000-0002-7059-1884
dc.language.isoen
dc.relation.ispartofPharmaceuticals
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectEndometrial Cancer
dc.subjectHydrazone
dc.subjectMolecular Docking
dc.subjectMtor
dc.subjectSpheroid
dc.titleMtor pathway inhibition, anticancer activity and in silico calculations of novel hydrazone derivatives in two- and three-dimensional cultured type 1 endometrial cancer cells
dc.typeArticle

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