Protocatechuic acid and alkyl esters: antioxidants properties and their effects on oxidative metabolism of leukocytes

Abstract

Excessive production of reactive oxygen species(ROS) results in oxidative stress, a deleterious process that can cause damage to cellular structures and to their constituents, including lipids and membranes, proteins and DNA. On the other hand, there is clear evidence of the physiological and essential role of ROS through its participation in cell signaling pathways. Additionally, the pro-oxidant effects, i.e., processes that can exacerbate the intracellular production of ROS, are often part of the mechanism of pharmacological action of chemotherapeutic agents. Protocatechuic acid (3,4-dihydroxybenzoic acid), a benzoic acid derivative, has been drawing attention since it has both antioxidant and pro-oxidant activity. In a dose dependent way, besides displaying a protective effect of against oxidative stress, it has anticancer properties by causing apoptosis or delay the invasion and metastasis in several types of cancer cells. Recent studies have shown that anti or pro-oxidant properties of polyphenols and their effects on cell cultures may depend on their lipophilicity in addition to their redox characteristics. Thus, this project aims to study the chemical properties and biological effects of esters of the protocatechuic acid in leukocytes and search for correlation among redox features, lipophilicity and biological activity. Alkyl esters of 1, 4, 7 and 10 carbons will be synthesized and studied regarding: anti and pro-oxidant potential in chemical models, inhibition of neutrophil peroxidase, inhibition of oxidative burst of neutrophils and modulation of cytokine production.