Kinetic studies of reactions mediated by oxidants produced by neutrophils: mechanism of deleterious action and development of enzyme inhibitors

• Grant number: 13/08784-0
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2014
• End date: January 31, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Enzymology
• Principal Investigator: Valdecir Farias Ximenes
• Grantee: Valdecir Farias Ximenes
• Host Institution: Faculdade de Ciências (FC). Universidade Estadual Paulista (UNESP). Campus de Bauru. Bauru , SP, Brazil

Abstract

Mounting evidence has demonstrated the role of hypohalous acids as hypochlorous acid (HOCl) and hypobromous acid (HOBr) as agents involved in biomolecules degradation. Indeed, the identification of biomarkers as chlorotyrosine and HOCl and HOBr modified proteins and nucleic acid has been widely demonstrated and correlated with pathologies as Alzheimer`s disease, Parkinson`s disease, chronic obstructive pulmonary disease among others. In the same direction, inhibitors of the enzymes involved directly or indirectly in the biosynthesis of these oxidants are current targets for the developments of new drugs. This project has as objective the kinetic study and, as a consequence, shed a light on the mechanism of these biologically relevant reactions. We aim to continue studies that are in development in our laboratory, but now with a deeper chemical point of view, it means, measuring the chemical reactivity. The central theme is to measure, using fast kinetic technology (Stopped-Flow), the rate constants of the reactions and elucidate their mechanism and relevance in the biological medium. Among the reactions that we aim to study are included: reactivity of HOCl, HOBr and their haloamines taurine chloramine and bromamine with nucleosides; studies of protein aggregation (formation of amyloidal protein) provoked by its oxidation; myeloperoxidase inhibition by 4-aminochalcones and correlates compounds, looking for the rate constants between the redox active forms of MPO and the inhibitors; inhibition of NADPH oxidase by esters of phenolic acids (determination of rate constants); studies of the reactivity between apocynin free radicals and sulfhydryl groups. We believe that these studies will result in a deeper understanding of these deleterious reactions and the development of inhibitors for the involved enzymes, as we hope to demonstrate in the project. (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PARACATU, LUANA C.; ZERAIK, MARIA L.; BERTOZO, LUIZA DE CARVALHO; BARTOLOMEU, ALOISIO DE ANDRADE; DA SILVA FILHO, LUIZ C.; DA FONSECA, LUIZ M.; XIMENES, VALDECIR F.. Synthesis, Antioxidant and Anti-inflammatory Properties of an Apocynin- Derived Dihydrocoumarin. Medicinal Chemistry, v. 13, n. 1, p. 93-100, 2017. (13/07600-3, 13/08784-0)

DE VASCONCELOS, DEBORA NALIATI; XIMENES, VALDECIR FARIAS. Albumin-induced circular dichroism in Congo red: Applications for studies of amyloid-like fibril aggregates and binding sites. SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY, v. 150, p. 321-330, NOV 5 2015. (13/08784-0)

VENTURINI, DIEGO; PASTRELLO, BRUNA; ZERAIK, MARIA LUIZA; PAULI, IVANI; ANDRICOPULO, ADRIANO DEFINI; SILVA-FILHO, LUIZ CARLOS; BOLZANI, V. S.; MORGON, NELSON HENRIQUE; DA SOUZA, A. R.; XIMENES, VALDECIR FARIAS. Experimental, DFT and docking simulations of the binding of diapocynin to human serum albumin: induced circular dichroism. RSC ADVANCES, v. 5, n. 76, p. 62220-62228, 2015. (11/03017-6, 13/07600-3, 13/08784-0)

ZERAIK, MARIA LUIZA; PETRONIO, MAICON S.; COELHO, DYOVANI; REGASINI, LUIS OCTAVIO; SILVA, DULCE H. S.; DA FONSECA, LUIZ MARCOS; MACHADO, SERGIO A. S.; BOLZANI, VANDERLAN S.; XIMENES, VALDECIR F.. Improvement of Pro-Oxidant Capacity of Protocatechuic Acid by Esterification. PLoS One, v. 9, n. 10, OCT 23 2014. (11/03017-6, 13/07600-3, 13/08784-0)

BERTOZO, LUIZA DE CARVALHO; MORGON, NELSON HENRIQUE; DE SOUZA, AGUINALDO ROBINSON; XIMENES, VALDECIR FARIAS. Taurine Bromamine: Reactivity of an Endogenous and Exogenous Anti-Inflammatory and Antimicrobial Amino Acid Derivative. BIOMOLECULES, v. 6, n. 2, JUN 2016. (13/08784-0)

PASTRELLO, BRUNA; PARACATU, LUANA CHIQUETTO; BERTOZO, LUIZA DE CARVALHO; MARTINEZ PAINO, IEDA MARIA; LISBOA-FILHO, PAULO NORONHA; XIMENES, VALDECIR FARIAS. Synthesis and evaluation of the potential deleterious effects of ZnO nanomaterials (nanoneedles and nanoflowers) on blood components, including albumin, erythrocytes and human isolated primary neutrophils. JOURNAL OF NANOPARTICLE RESEARCH, v. 18, n. 7, JUL 30 2016. (13/08784-0)