title: Antiradical, chelating and antioxidant activities of hydroxamic acids and hydroxyureas.
abstract: Reactive oxygen species, along with reactive nitrogen species, may play an important role in the pathogenesis and progress of many diseases, including cancer, diabetes and sickle cell disease. It has been postulated that hydroxyurea, one of the main treatments in sickle cell disease, achieves its activity partly also through its antioxidant properties. A series of hydroxyurea derivatives of L- and D-amino acid amides and cycloalkyl-N-aryl-hydroxamic acids was synthesized and investigated for their radical scavenging activity, chelating properties and antioxidant activity. All the compounds showed exceptional antiradical activities. For example, free radical scavenging activities of investigated hydroxyureas were higher than the activity of standard antioxidant, butylated hydroxyanisole (BHA). Moreover, most of the investigated hydroxamic acids were stronger Fe²⁺ ion chelators than quercetin. In addition, the investigated compounds, especially hydroxamic acids, were proven to be excellent antioxidants. They were as effective as BHA in inhibiting β-carotene-linoleic acid coupled oxidation. It is reasonable to assume that the antioxidant activity of the investigated compounds could contribute to their previously proven biological properties as cytostatic and antiviral agents.
authors.affiliation: Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, Zagreb HR-10000, Croatia. mzovko@pharma.hr
authors.forename: Marijana Zovko
authors.initials: MZ
authors.lastname: Končić
authors.forename: Monika
authors.initials: M
authors.lastname: Barbarić
authors.forename: Ivana
authors.initials: I
authors.lastname: Perković
authors.forename: Branka
authors.initials: B
authors.lastname: Zorc
mesh_terms: D000755:Anemia, Sickle Cell / Q000188:drug therapy / Q000503:physiopathology; D001713:Biphenyl Compounds / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D006918:Hydroxyurea / Q000138:chemical synthesis / Q000494:pharmacology*; D007501:Iron / Q000037:antagonists & inhibitors / Q000378:metabolism; D007502:Iron Chelating Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D019787:Linoleic Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D010084:Oxidation-Reduction / Q000187:drug effects*; D010851:Picrates / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013055:Spectrophotometry, Infrared; D019207:beta Carotene / Q000378:metabolism
chemical_list: D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D006877:Hydroxamic Acids; D007502:Iron Chelating Agents; D010851:Picrates; D017382:Reactive Oxygen Species; D019207:beta Carotene; D002084:Butylated Hydroxytoluene; D002083:Butylated Hydroxyanisole; D019787:Linoleic Acid; C004931:1,1-diphenyl-2-picrylhydrazyl; D007501:Iron; D006918:Hydroxyurea