Integrated Experimental and Preliminary In Silico Study of Myrtenyl Dihydrocaffeate: Biocatalytic Synthesis...

Dihydrocaffeic acid (DHCA) is a naturally occurring phenolic acid with recognized antioxidant and biological properties. However, its relatively high polarity limits its applicability in lipid-based systems. In this study, myrtenyl dihydrocaffeate was synthesized through lipase-catalyzed esterification of DHCA with myrtenol using immobilized Candida antarctica lipase B. The reaction conditions were optimized using response surface methodology based on a central composite design, yielding an experimental ester yield of 39.94 ± 1.16%. The synthesized ester was characterized by NMR spectroscopy and subsequently evaluated using a combination of experimental and in silico approaches. Antioxidant activity was determined by DPPH^• and ABTS^•+ radical scavenging assays, while oxidative stabilization of rapeseed oil was assessed by pressure differential scanning calorimetry (PDSC). Antimicrobial activity was evaluated using disk diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays. In silico studies included ADMET profiling, PASS bioactivity prediction, protein target prediction, and molecular docking. These computational analyses were used only as hypothesis-generating tools because the predicted protein targets had low target-probability scores and were not experimentally validated. Myrtenyl dihydrocaffeate retained substantial antioxidant activity and significantly improved the oxidative stability of rapeseed oil, exhibiting protection factors comparable to those of DHCA. The ester also demonstrated mild antimicrobial activity against selected Gram-positive bacteria. Overall, the results indicate that lipophilization of DHCA with myrtenol is an effective strategy for developing lipophilic antioxidant derivatives for lipid-based food, cosmetic, or topical formulations, while the predicted molecular targets require experimental validation.