Synthesis and antioxidant activity of long chain alkyl hydroxycinnamates

Long chain alkyl hydroxycinnamates (8–21) were synthesized from the corresponding half esters of malonic acid (5–7) and benzaldehyde derivatives by Knoevenagel condensation. The total antioxidant capacity of these hydroxycinnamyl esters was evaluated using DPPH and ABTS assays. The observed antioxidant activity was highest for esters of caffeic acid followed by sinapic esters and ferulic esters. The parameters for drug-likeness of these hydroxycinnamyl esters were also evaluated according to the Lipinski’s ‘rule-of-five’. All the ester derivatives were found to violate one of the Lipinski’s parameters (cLogP >5), even though they have been found to be soluble in protic solvents. The predictive topological polar surface area (TPSA) data allow concluding that they could have a good capacity for penetrating cell membranes. Therefore, one can propose these novel lipophilic compounds as potential antioxidants for tackling oxidative processes.

Graphical abstractLong chain alkyl hydroxy cinnamates (8–21) were synthesized from the corresponding half esters of malonic acid (5–7) and benzaldehyde derivatives by Knoevenagel condensation. The antioxidant activity was highest for esters of caffeic acid followed by sinapic and ferulic esters. The parameters for drug-likeness of these hydroxycinnamyl esters were also evaluated.Figure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► Synthesis of long chain alkyl hydroxy cinnamates from the corresponding half esters of malonic acid and benzaldehyde derivatives by Knoevenagel condensation. ► Evaluation of the total antioxidant capacity of hydroxycinnamyl esters throughout DPPH and ABTS assays. The observed antioxidant activity was highest for esters of caffeic acid followed by sinapic esters and ferulic esters. ► Evaluation of drug-likeness of hydroxycinnamyl esters in accordance to the Lipinski’s ‘rule-of-five’. All the ester derivatives were found to violate one of the Lipinski’s parameters (cLogP >5), even though they have been found to be soluble in protic solvents. ► Prediction of the topological polar surface area (TPSA) data allows concluding that hydroxycinnamyl esters could have a good capacity for penetrating cell membranes. ► The overall research allow to develop novel lipophilic antioxidants for tackling oxidative processes.