Synthesis, Epoxidation, and Cytotoxic Evaluation of Oleic Acid Amide Derivatives as Anticancer Agents: In Vitro, Molecular Docking, and Molecular Dynamics Studies

ABSTRACT Fatty acid methyl ester (FAME) was successfully isolated from palm oil via transesterification, followed by purification using the urea inclusion method and hydrolysis to yield oleic acid. The oleic acid was converted into two amide derivatives, that is, N,N‐ diethyloleamide and N ‐propyloleamide, through amidation reaction with diethylamine and propylamine, respectively. Both amides were subsequently epoxidized with performic acid at room temperature to yield their respective epoxides. Structural characterization was performed using FTIR, GC‐MS/LC‐MS, 1 H‐NMR, and 1 3 C‐NMR techniques. The anticancer potential of the synthesized compounds was assessed in vitro using the MTT assay on breast cancer (T47D), cervical cancer (HeLa), and normal (Vero) cell lines. The compounds exhibited significant cytotoxicity, with IC 50 values ranging from 22.85 to 36.96 µg/mL for T47D and from 21.07 to 92.83 µg/mL for HeLa. Selectivity index analysis showed favorable cancer cell selectivity, with values reaching up to 6.78. Molecular docking against the thioesterase domain of fatty acid synthase demonstrated strong binding affinities, ranging from −4.26 to −4.68 kcal/mol, while molecular dynamics simulations suggested that some non‐covalent interactions remained with a MM‐PBSA energy of –28.84 ± 2.70 kcal/mol. These findings highlight the potential of oleic acid‐derived amide and epoxide derivatives as promising selective anticancer agents for further investigation.