title: Antioxidant properties of hydroxycinnamic acids: a review of structure- activity relationships.
abstract: Hydroxycinnamic acids (HCAs) are important phytochemicals possessing significant biological properties. Several investigators have studied in vitro antioxidant activity of HCAs in detail. In this review, we have gathered the studies focused on the structure-activity relationships (SARs) of these compounds that have used medicinal chemistry to generate more potent antioxidant molecules. Most of the reports indicated that the presence of an unsaturated bond on the side chain of HCAs is vital to their activity. The structural features that were reported to be of importance to the antioxidant activity were categorized as follows: modifications of the aromatic ring, which include alterations in the number and position of hydroxy groups and insertion of electron donating or withdrawing moieties as well as modifications of the carboxylic function that include esterification and amidation process. Furthermore, reports that have addressed the influence of physicochemical properties including redox potential, lipid solubility and dissociation constant on the antioxidant activity were also summarized. Finally, the pro-oxidant effect of HCAs in some test systems was addressed. Most of the investigations concluded that the presence of ortho-dihydroxy phenyl group (catechol moiety) is of significant importance to the antioxidant activity, while, the presence of three hydroxy groups does not necessarily improve the activity. Optimization of the structure of molecular leads is an important task of modern medicinal chemistry and its accomplishment relies on the careful assessment of SARs. SAR studies on HCAs can identify the most successful antioxidants that could be useful for management of oxidative stress-related diseases.
authors.affiliation: Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, PO Box 71345-3388, Shiraz, Iran. firuzio@sums.ac.ir.
authors.forename: N
authors.initials: N
authors.lastname: Razzaghi-Asl
authors.forename: J
authors.initials: J
authors.lastname: Garrido
authors.forename: H
authors.initials: H
authors.lastname: Khazraei
authors.forename: F
authors.initials: F
authors.lastname: Borges
authors.forename: O
authors.initials: O
authors.lastname: Firuzi
mesh_terms: D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology*; D003373:Coumaric Acids / Q000737:chemistry* / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D003373:Coumaric Acids; D017382:Reactive Oxygen Species