Low-toxicity biocatalytic platform for efficient synthesis of cytoselective vanillyl ricinoleate with anticancer...

Vanillyl compounds are natural bioactives, but their pungency and low bioavailability limit practical use. To overcome these issues, non-pungent vanillyl esters have been developed. However, their suitability for industrial applications as bioactive materials is questionable due to toxicity concerns arising from raw materials and residues. To address this unmet need, castor oil, a renewable non-edible feedstock rich in ricinoleic acid, was utilized to develop a low-toxicity solvent platform that supports efficient biocatalysis while minimizing environmental impact. In this study, vanillyl ricinoleate was synthesized using low-toxicity materials including castor oil and assessed for cytotoxicity in normal (L929) and cancer (HCT116, HT-29) cells to evaluate its anticancer potential. Vanillyl alcohol and castor oil were used as reagents, with 2-heptanone as the solvent, a safety-verified compound permitted for direct addition in foods. The reaction was catalyzed by Novozym 435, which is widely used and safety-verified across various industrial applications. Under these conditions, 94.46% yield was achieved within 6 h. The half-inhibitory concentration (IC₅₀) was 198.74 μM in L929 cells and 83.63 μM and 74.27 μM in HCT116 and HT-29 cells, respectively. These findings support the anticancer potential of vanillyl ricinoleate and demonstrate the feasibility of producing it efficiently from safe materials, providing a practical route toward industrially applicable non-pungent vanillyl bioactives.