Evaluation of ۲(۳H)-Benzoxazolone Derivatives Containing Piperidine Substituents as Cytotoxic and Apoptotic Agents: An in vitro and in silico Study

To create chemical structures with various pharmacological actions, heterocyclic compounds play a key role as pharmacophores. The pharmacological effects of derivatives of ۲(۳H)-benzoxazolone include analgesic, anti-inflammatory, antibacterial, anti-nociceptive, and anticancer activities. The aim of this study was to examine the cytotoxic and apoptotic effects of newly synthesized ۲(۳H)-benzoxazolone derivatives against metastatic MDA-MB-۲۳۱ breast cancer cell lines in vitro and in silico. The structural verifications of target compounds were performed by elemental analysis, FT-IR, and NMR spectra. MTT assay was used to assess the cytotoxic effects of the compounds in terms of the decreased cell viability. TUNEL assay was used to confirm the apoptotic activities of the compounds. The MTT results revealed that compound ۲, which has a chlorine substituent at the ۵th position of the core structure, had the maximum activity at a concentration of ۵۰ µM during a ۷۲-hour incubation period. The results demonstrated that ۲(۳H)-benzoxazolone derivatives with piperidine substituents efficiently reduced the cell survival in the target cell line. The molecular docking results also supported the experimental data. Furthermore, the in-silico investigation demonstrated that the synthesized compounds have desirable drug-like characteristics for the oral drug-delivery system. In addition, the findings showed that chlorination of the benzoxazolone ring influences the apoptotic activity, suggesting that these derivatives might be promising innovative anticancer medications in the future.