Some Benzoxazole Derivatives as Potential mTOR Inhibitors: Anticancer Activity and Molecular Docking Studies in Breast Cancer

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options, highlighting the need for novel targeted therapies. The mechanistic target of rapamycin (mTOR) is a key regulator of cancer cell proliferation and survival, making it an attractive target for drug development. Based on this, we investigated the anticancer effects of four previously synthesized benzoxazole derivatives—2-(4-isopropylphenyl)-5-nitrobenzoxazole (i), 2-(2,3-dimethylphenyl)-6-nitrobenzoxazole (ii), 2-(2,4-dimethylphenyl)-5-nitrobenzoxazole (iii), and 2-(2,4-dimethylphenyl)-6-nitrobenzoxazole (iv)—through in vitro cytotoxicity assays and molecular docking studies. The cytotoxic effects of the compounds were evaluated using the MTT assay on MDA-MB-231 cells, which were treated with different concentrations (0–100 µM) for 48 hours. To further explore the mechanism of action, molecular docking was performed using mTOR as the target. There was a dose-dependent reduction in cell viability, with compound ii exhibiting the highest cytotoxic activity (IC50= 40.99±0.06 µM). According to molecular docking, all compounds demonstrated strong binding interactions with key residues such as Trp2239, Lys2187, Asp23357, and Val2240, as well as coordination with magnesium ions, supporting their role as mTOR inhibitors. Our results revealed that these benzoxazoles could function as potential candidates for exerting their anticarcinogenic effects on MDA-MB-231 cells through mTOR inhibition. © 2025, Bursa Uludağ University Faculty of Medicine. All rights reserved.