Synthesis and In Vitro/In silico Evaluation of Novel 2-Aryl-6-carboxamide-Substituted Benzoxazole Derivatives with Anticancer Effects and mTOR Inhibitory Potential
ACS Omega, cilt.11, sa.22, ss.32096-32117, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 11 Sayı: 22
- Basım Tarihi: 2026
- Doi Numarası: 10.1021/acsomega.5c12045
- Dergi Adı: ACS Omega
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Directory of Open Access Journals
- Sayfa Sayıları: ss.32096-32117
- Sivas Cumhuriyet Üniversitesi Adresli: Evet
Özet
In this study, we synthesized novel 2-aryl-6-carboxamide-substituted benzoxazole derivatives and evaluated their anticancer potential against breast cancer cell lines, with a focus on mTOR inhibitory activity. The compounds were synthesized via a three-step method and characterized by NMR analysis. In silico studies─including molecular docking, molecular dynamics simulations, and ADMET predictions─were conducted to predict interactions with the target protein and support the observed biological activity. IC50 values were determined in MCF-7 and MDA-MB-231 cells, with MCF-7 cells exhibiting greater sensitivity to the compound. The most active compounds, COH-17 and COH-19, demonstrated cytotoxicity as indicated by LDH release assays. Apoptotic effects were investigated at both molecular and cellular levels: Western blot analysis assessed key apoptotic proteins (Bcl-2, Bax, caspase-3, and p53), while RT-qPCR quantified the expression of BRCA1, BRCA2, PTEN, TP53, BCL-2, BAX, Caspase-3, PI3K, AKT, and BRAD1 genes. Morphological changes associated with apoptosis were confirmed by DAPI staining and fluorescence microscopy, and early and late apoptosis were quantified using Annexin V-FITC/PI flow cytometry. Cell cycle analysis revealed phase-specific arrest, further supporting the antiproliferative activity of the compound. Overall, COH-17 and COH-19 demonstrated potent anticancer effects through mTOR inhibition, induction of apoptosis, and cell cycle arrest, highlighting their potential as targeted therapeutic agents for breast cancer.