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Master's Dissertation
DOI
Document
Author
Full name
Filipe André Nascimento Silva
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2010
Supervisor
Committee
Pereira, Claudio Martin Pereira de (President)
Quina, Frank Herbert
Trossini, Gustavo Henrique Goulart
Title in Portuguese
Avaliação antioxidante de 3,5-dimetil isoxazol, pirazóis e tiazóis utilizando o método ORAC (capacidade de absorção de radicais oxigênio)
Keywords in Portuguese
Antioxidantes
Antioxidantes sintéticos
ORAC
Pirazóis
Tiazóis
Abstract in Portuguese
Os radicais livres são espécies químicas que reagem rapidamente com diversos compostos e alvos celulares, por possuírem tempo de meia vida muito curto e serem espécies altamente instáveis. A formação destes compostos constitui uma ação contínua e fisiológica, cumprindo funções biológicas essenciais as quais ocorrem pela perda ou adição de um único elétron a um composto não radicalar. Estas reações podem ocorrer em processos bioquímicos do sistema imune ou químicos, causando prejuízo às células através da destruição de componentes, como proteínas, lipídios, açúcares e nucleotídeos. Sabe-se que existem compostos que são efetivos contra tais espécies, prevenindo os danos provocados pelo estresse oxidativo. O objetivo deste trabalho foi estudar compostos heterocíclicos que possuam nitrogênio em sua estrutura (azóis), que figuram na literatura como moléculas exemplares de compostos de aplicação farmacológica de amplo espectro. Dentre estes compostos foram analisados os derivados de pirazóis (26 compostos), tiazóis (7 compostos) e 1 isoxazol (3,5-dimetilisoxazol). Estes 34 compostos foram avaliados pela metodologia ORAC (Capacidade de Absorção de Radicais Oxigênio) a fim de determinar e/ou de avaliar seu potencial antioxidante. A escolha do método ORAC se deu pelo fato das moléculas estudadas apresentarem características hidrofílicas e lipofílicas, além de ser um método validado pela literatura, disponível e de ampla aplicação. O método ORAC avalia a capacidade antioxidante da amostra, medindo sua habilidade de proteger a fluoresceína (FL) da oxidação pelo AAPH no meio reacional. O AAPH é um gerador de radicais livres que a 37°C retira hidrogênio do meio, promovendo a redução da fluorescência da fluoresceína em λ medido pelo tempo. Seis compostos apresentaram atividade antioxidante de boa à moderada: 3,5-dimetil-1H-pirazol (2.382 µmol eq.Trolox/g); 3-fenil-5-(4-fluorfenil)-1-tiocarbamoil-4,5-diidro-1H-pirazol (6.354 µmol eq.Trolox/g); 3-fenil-5-(2-metoxifenil)-1-tiocarbamoil-4,5-diidro-1H-pirazol (8.739 µmol eq.Trolox/g); 5-(2,4-diclorofenil)-3-fenil-1-tiocarbamoil-4,5-diidro-1H-pirazol (6.022,226 µmol eq.Trolox/g); 2-[5-(4-metoxifenil)-3-fenil-4,5-diidro-1H-pirazol-1-il]-4-feniltiazol (3.135 µmol eq.Trolox/g); e finalmente 2-[5-(3-nitrofenil)-3-fenil-4,5-diidro-1H-pirazol-1-il]-4-feniltiazol (2.700 µmol eq.Trolox/g). Os experimentos com o método ORAC para os azóis estudados apresentaram reprodutibilidade na execução experimental e demonstraram ser uma alternativa viável para estudos de moléculas sintéticas de potencial antioxidante.
Title in English
Evaluation of antioxidant 3,5-dimethyl isoxazol pyrazoles and thiazoles using the ORAC method (absorption capacity oxygen radical)
Keywords in English
Antioxidants
ORAC
Pyrazoles
Synthetic antioxidants
Thiazoles
Abstract in English
Free radicals are chemical species that react rapidly with various compounds and target cells, as they have a very short half life and are highly unstable. The formation of these compounds consists of a continuous, physiological action, which includes essential biological functions and occurs through the loss or addition of a single electron to a non-radical compound. These reactions may occur in biochemical processes of the immune system, or by chemical reactions, causing damage to the cells through the destruction of components such as proteins, lipids, sugars and nucleotides. It is known that compounds exist which are effective against these species, preventing damage caused by oxidative stress. The object of this work was to study heterocyclic compounds that have nitrogen in their structure (azoles), which appear in the literature as exemplary molecules of compounds with a wide spectrum of pharmacological applications. Of these compounds, derivatives of pyrazoles (26 compounds), thiazoles (7 compounds) and 1 isoxazole (3,5-dimethylisoxazole) were analyzed. These 34 compounds were evaluated by the ORAC (Oxygen Radicals Absorption Capacity) in order to determine and/or evaluate its antioxidant potential. The choice of ORAC method is based on the fact that the molecules studied have hydrophilic and lipophilic characteristics, as well as a method validated by the literature, which is available and widely used. The ORAC method evaluates the antioxidant capacity of the sample, measuring its ability to protect the fluorescence (FL) of the oxidation by the AAPH in the reaction medium. AAPH is a generator of free radicals which, at 37°C, removes hydrogen from the medium, promoting the reduction of fluorescence from fluorescein in λ measured by time. Six compounds present good to moderate antioxidant activity: 3,5-dimethyl-1H-pyrazole (2.382 µmol eq.Trolox/g); 3-phenyl-5-(4-fluorphenyl)-1-thiocarbamoyl-4,5-dihydro-1H-pyrazole (6.354 µmol eq.Trolox/g); 3-phenyl-5-(2-methoxyphenyl)-1-thiocarbamoyl-4,5-dihydro-1H-pyrazole (8.739 µmol eq.Trolox/g); 5-(2,4-diclorophenyl)-3-phenyl-1-thiocarbamoyl-4,5-dihydro-1H-pyrazole (6.022,226 µmol eq.Trolox/g); 2-[5-(4-methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazole-1-il]-4-phenylthiazole (3.135 µmol eq.Trolox/g); and finally, 2-[5-(3-nitrophenyl)-3-phenyl-4,5-dihydro-1H-pyrazole-1-il]- 4-phenylthiazole (2.700 µmol eq.Trolox/g). Experiments with the ORAC method for the azoles studied present reproducibility in the experimental execution, and have proven to be a viable alternative for studies of synthetic molecules with antioxidant potential.
 
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Publishing Date
2011-06-27
 
WARNING: The material described below relates to works resulting from this thesis or dissertation. The contents of these works are the author's responsibility.
  • PEREIRA, Claudio M. P, et al. Synthesis of 4-iodopyrazoles: A Brief Review. Mini-Reviews in Organic Chemistry., 2008, vol. 5, n. 4, p. 331-335.
  • SILVA, Filipe André Nascimento, et al. Antioxidant capacity of 2-(3,5-diaryl-4,5-dihydro-1H-pyrazol-1-yl)-4-phenylthiazoles. Letters in Drug Design & Discovery, 2010, vol. 7, p. 657-660.
  • SILVA, Filipe André Nascimento, et al. Ultrasound Promoted Large-Scale Preparation in Aqueous Media and Antioxidant Activity of Azoles. Letters in Drug Design & Discovery, 2009, vol. 6, p. 323-326.
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