Synthesis and antioxidant activity of long chain alkyl hydroxycinnamates

• Published in: European journal of medicinal chemistry Vol. 46; no. 2; pp. 773 - 777
• Main Authors: Menezes, Jose C.J.M.D.S., Kamat, Shrivallabh P., Cavaleiro, Jose A.S., Gaspar, Alexandra, Garrido, Jorge, Borges, Fernanda
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 01.02.2011; Elsevier
• Subjects: Alkyl hydroxycinnamates; Antioxidant activity; Antioxidants - chemical synthesis; Antioxidants - chemistry; Biological and medical sciences; Caffeic acid; Chemistry, Medicinal; Cinnamates - chemical synthesis; Cinnamates - chemistry; Drug-likeness properties; Ferulic acid; Life Sciences & Biomedicine; Medical sciences; Miscellaneous; Molecular Structure; Oxidation-Reduction; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; Sinapic acid; Stereoisomerism; Sinapic acid; Alkyl hydroxycinnamates; Drug-likeness properties; Antioxidant activity; Caffeic acid; Ferulic acid; MALONIC-ACID; PROFILE; ESTERS; DERIVATIVES; CONSTITUENTS; DPPH; Phenolic acid; Knoevenagel condensation; Long chain; Antioxidant; Radical scavenger; Biological activity; Cinnamic acid derivatives; Chemical synthesis
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2010.12.016

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. Long 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. [Display omitted] ► 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.