title: Free radical scavenging and COX-2 inhibition by simple colon metabolites of polyphenols: A theoretical approach.
abstract: Free radical scavenging and inhibitory potency against cyclooxygenase-2 (COX-2) by two abundant colon metabolites of polyphenols, i.e., 3-hydroxyphenylacetic acid (3-HPAA) and 4-hydroxyphenylpropionic acid (4-HPPA) were theoretically studied. Different free radical scavenging mechanisms are investigated in water and pentyl ethanoate as a solvent. By considering electronic properties of scavenged free radicals, hydrogen atom transfer (HAT) and sequential proton loss electron transfer (SPLET) mechanisms are found to be thermodynamically probable and competitive processes in both media. The Gibbs free energy change for reaction of inactivation of free radicals indicates 3-HPAA and 4-HPPA as potent scavengers. Their reactivity toward free radicals was predicted to decrease as follows: hydroxyl>>alkoxyls>phenoxyl≈peroxyls>>superoxide. Shown free radical scavenging potency of 3-HPAA and 4-HPPA along with their high μM concentration produced by microbial colon degradation of polyphenols could enable at least in situ inactivation of free radicals. Docking analysis with structural forms of 3-HPAA and 4-HPPA indicates dianionic ligands as potent inhibitors of COX-2, an inducible enzyme involved in colon carcinogenesis. Obtained results suggest that suppressing levels of free radicals and COX-2 could be achieved by 3-HPAA and 4-HPPA indicating that these compounds may contribute to reduced risk of colon cancer development.
authors.affiliation: Department of Biology, Josip Juraj Strossmayer University of Osijek, Cara Hadrijana 8a, 31000 Osijek, Croatia.
authors.forename: Ana
authors.initials: A
authors.lastname: Amić
authors.affiliation: Department of Chemical-Technological Sciences, State University of Novi Pazar, Vuka Karadžića bb, 36300 Novi Pazar, Serbia.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Marković
authors.affiliation: Faculty of Physical Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia.
authors.forename: Jasmina M Dimitrić
authors.initials: JMD
authors.lastname: Marković
authors.affiliation: Department of Chemical-Technological Sciences, State University of Novi Pazar, Vuka Karadžića bb, 36300 Novi Pazar, Serbia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Jeremić
authors.affiliation: NMR Center, Ruđer Bošković Institute, P.O. Box 180, 10002 Zagreb, Croatia.
authors.forename: Bono
authors.initials: B
authors.lastname: Lučić
authors.affiliation: Faculty of Agriculture, Josip Juraj Strossmayer University of Osijek, Kralja Petra Svačića 1d, 31000 Osijek, Croatia. Electronic address: damic@pfos.hr.
authors.forename: Dragan
authors.initials: D
authors.lastname: Amić
mesh_terms: D003106:Colon / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D059808:Polyphenols / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016166:Free Radical Scavengers; D059808:Polyphenols
keywords: 3-Hydroxyphenylacetic acid; 4-Hydroxyphenylpropionic acid; COX-2; DFT; Docking; Free radical scavenging