Design, Synthesis, and Biological Evaluation of Capsiate Analogues as Potential Bioactive Lipids

ABSTRACT Capsiates are lipid‐based compounds derived from natural products that have many interesting biological properties. In this study, a series of novel capsiate derivatives was synthesized from vanillyl ( 8a–g ) and coniferyl ( 13a–g ) alcohols employing fatty acids containing oxadiazole functionality. Employing reported protocols, 14 analogues were prepared and their structures were confirmed with 1 H, 13 C NMR, and mass spectral studies. The synthesized compounds were evaluated for their antioxidant, antimicrobial, and anti‐inflammatory activities. Results showed that the analogues with methoxy substitutions ( 13f–h ) exhibited good antioxidant activity, which was higher compared with reference compounds such as BHT and alpha‐tocopherol. The compounds exhibited moderate antimicrobial activity, with compound 8b showing a broad spectrum of activity against all the tested organisms. In the anti‐inflammatory activity, they were able to scavenge NO‐free radicals produced in response to lipopolysaccharide (LPS) treatment. The capsiate derivatives 8f , 8g , 13b , and 13e have shown significant anti‐inflammatory and anti‐oxidant properties. Overall, it was observed that capsiate derivatives from coniferyl exhibited higher activity compared to vanillyl derivatives. Practical Applications : Novel capsiate heterocyclic hybrids are reported as potential bioactive lipids. This new class of hybrid molecules exhibited potent antioxidant and anti‐inflammatory activity, as well as promising antimicrobial properties. The products exhibited potent antioxidant activity, which was superior to reference compounds. They can be utilized as potential antioxidative agents in formulations.