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Nitrones and hydroxylamines with pharmacological properties: synthesis, exploration of antioxidant activity and cellular studies


It has been postulated that the accumulation of oxidized proteins and damaged mitochondrial DNA are factors that contribute actively to the aging process. The physiological response to aging is the exponential increase in the incidence of heart attacks, strokes, cancer, Alzheimer's and Parkinson's diseases. Although there is no link between these diseases, experimental evidence indicates that radical species are actively involved in triggering them. The main objective of this project is to synthesize new molecules containing the nitrone and hydroxylamine functional groups, which have pharmacological activity against models of diseases related to oxidative stress. This project focuses on the applied organic synthesis, taking into account the pharmacological and mercadological aspects of drug designing, whose core is to employ a strategic approach where amino acids, peptides and commercial drugs will be used as synthetic platforms. Since the physiological and pharmacological effects of nitrones and hydroxylamines are not established, studies comparing this library of new molecules with standard nitrones, hydroxylamines and antioxidants species will be done to evaluate the structure / pharmacological activity of these new molecules according to degree of protection offered when a cellular model is exposed to induced oxidative damage. (AU)

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Scientific publications
(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)
CARNEIRO, LEONARDO M.; BARTOLONI, FERNANDO H.; ANGOLINI, CELIO F. F.; KEPPLER, ARTUR F.. Solvent-free synthesis of nitrone-containing template as a chemosensor for selective detection of Cu(II) in water. SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY, v. 267, n. 2, . (12/07717-5, 12/13807-7)
MATIAS, A. C.; BIAZOLLA, G.; CERCHIARO, G.; KEPPLER, A. F.. alpha-Aryl-N-aryl nitrones: Synthesis and screening of a new scaffold for cellular protection against an oxidative toxic stimulus. Bioorganic & Medicinal Chemistry, v. 24, n. 2, p. 232-239, . (12/01397-9, 12/07717-5, 14/15534-3)
MAMUD, JULIA F.; BIAZOLLA, GIOVANNA; MARQUES, CAROLINE S.; CERCHIARO, GISELLE; DE QUEIROZ, THIAGO B.; KEPPLER, ARTUR F.; POLO, ANDRE S.. Z to E light-activated isomerization of alpha-pyridyl-N-arylnitrone ligands sensitized by rhenium(I) polypyridyl complexes. Inorganica Chimica Acta, v. 514, . (16/21993-6, 18/14152-0, 12/07717-5, 15/20007-5, 17/07289-7)

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Filed patent(s) as a result of this research project

USO DA ALFA-ARIL, N-ARIL NITRONAS PARA O TRATAMENTO E/OU PREVENÇÃO DE DOENÇAS DESENCADEDAS PELO ESTRESSE OXIDATIVO BR1020150289430 - Universidade Federal do ABC (UFABC) . Artur Franz Keppler ; Giselle Cerchiaro ; Giovanna Biazolla - November 2015, 18