Development of Benzoxazole Derivatives Targeting mTOR: A Promising Approach for Breast Cancer Therapy

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dc.contributor.authorAlagoz, Mehmet Abdullah
dc.contributor.authorResitoglu, Meryem Temiz
dc.contributor.authorKuzu, Burak
dc.contributor.authorSabrie, Zainab
dc.contributor.authorYetkin, Derya
dc.contributor.authorZobi, Cengiz
dc.contributor.authorTiftik, Rukiye Nalan
dc.date.accessioned2026-04-04T13:37:36Z
dc.date.available2026-04-04T13:37:36Z
dc.date.issued2025
dc.departmentİnönü Üniversitesi
dc.description.abstractClinical use of mTOR inhibitors in cancer treatment is well established due to the critical role of mTOR signaling in tumor progression. In this study, we report the structure-based design and biological evaluation of a series of benzoxazole derivatives as potential mTOR inhibitors. Cytotoxicity studies using MTT assays showed that compounds B4, B11, B12, and B20 exhibited significant antiproliferative effects against breast cancer cell lines with IC50 values between 4.96 and 9.82 mu M. Colorimetric enzymatic assays further revealed that among these, only B12 and B20 effectively inhibited mTOR phosphorylation at Ser2448 in MCF-7 cells. Additionally, both compounds modulated the expression of key apoptotic proteins, including Bax, caspase-3, p53, and Bcl2. Molecular docking studies against the 4JT5 protein demonstrated binding affinities with docking scores ranging from -7.084 to -7.426 kcal/mol, comparable to the reference compound P2X (-7.309 kcal/mol). Molecular dynamics simulations over 150 ns confirmed the stability of B12 and B20 in the active site, with an average RMSD of 2.8 & Aring; and 3.0 & Aring;, respectively. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the synthesized compounds were evaluated in silico. Among them, B4, B11, B12, and B20 exhibited drug-like characteristics and showed no undesirable toxic effects. These findings highlight the potential of B12 and B20 as lead compounds for the development of novel mTOR inhibitors in breast cancer therapy.
dc.description.sponsorshipInonu University [TCD-2021-2368]; Erzincan Binali Yimath;ldimath;rimath;m University Research Fund [TCD-2025-1019]
dc.description.sponsorshipThis work was financially supported by Inonu University-Research Project of TCD-2021-2368. The authors would also like to thank Mersin University Advanced Technology Education, Research and Application Center (MEITAM) for their valuable assistance and Erzincan Binali Y & imath;ld & imath;r & imath;m University Research Fund (Project no: TCD-2025-1019).
dc.identifier.doi10.1002/slct.202501424
dc.identifier.issn2365-6549
dc.identifier.issue21
dc.identifier.orcid0000-0003-1494-7652
dc.identifier.scopus2-s2.0-105007865367
dc.identifier.scopusqualityN/A
dc.identifier.urihttps://doi.org/10.1002/slct.202501424
dc.identifier.urihttps://hdl.handle.net/11616/109937
dc.identifier.volume10
dc.identifier.wosWOS:001499053600001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherWiley-V C H Verlag Gmbh
dc.relation.ispartofChemistryselect
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250329
dc.subjectApoptotic effect
dc.subjectBenzoxazole
dc.subjectMolecular docking
dc.subjectMTOR
dc.subjectStructure-activity relationship
dc.titleDevelopment of Benzoxazole Derivatives Targeting mTOR: A Promising Approach for Breast Cancer Therapy
dc.typeArticle

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