title: Novel quercetin derivatives: From redox properties to promising treatment of oxidative stress related diseases.
abstract: A set of O-substituted quercetin derivatives was prepared with the aim to optimize bioavailability and redox properties of quercetin, a known agent with multiple health beneficial effects. Electron-acceptor/-donor properties of the agents were evaluated theoretically by quantum chemical calculations and by experimental methods in cell-free model systems (2,2-diphenyl-1-picrylhydrazyl (DPPH) test, the ferric reducing ability of plasma (FRAP), peroxynitrite scavenging, protein-thiol oxidation) and in cellular systems of fibroblasts, microglials and cancer lines. The order of individual antioxidant effects varied dependently on the system used. In cellular systems, quercetin derivatives were shown to be better antioxidants compared to quercetin. Monochloropivaloylquercetin (CPQ), monoacetylferuloylquercetin (MAFQ) and chloronaphthoquinonequercetin (CHNQ) showed a prominent inhibitory effect on the key enzymes involved in diabetic complications, aldose reductase and α-glucosidase, suggesting their promising therapeutic application. In the cellular models of BHNF-3 fibroblasts, microglial cell line BV-2, colorectal cancer cell lines HCT-116 and HT-29, CHNQ and CPQ were studied for their cytotoxic, antiproliferative and antiinflammatory properties. In the rat model, CHNQ attenuated colon inflammation induced by acetic acid. In summary, our studies revealed CPQ and CHNQ as potential remedies of chronic age-related metabolic or inflammatory diseases, including diabetes and neurodegenerations. Furthermore, CHNQ represents a novel promising agent exerting its anticancer effect through induction of oxidative stress-dependent cell death.
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Petronela
authors.initials: P
authors.lastname: Zizkova
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Milan
authors.initials: M
authors.lastname: Stefek
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Lucia
authors.initials: L
authors.lastname: Rackova
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Marta
authors.initials: M
authors.lastname: Prnova
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia. Electronic address: Lubica.Horakova@savba.sk.
authors.forename: Lubica
authors.initials: L
authors.lastname: Horakova
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D011794:Quercetin
keywords: Aldose reductase; Anticancer and antiinflammatory effect; Antidiabetic; Ca(2+)-ATPase