Characterization of the electrochemical behaviour of antiinflammatory and antipsychotic drugs and their interaction with biomolecules within their respective pathways

• Ano de defesa: 2021
• Autor(a) principal: Prata, Raphael Bacil
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Biblioteca Digitais de Teses e Dissertações da USP
• Palavras-chave em Português: Anti-psicóticos atípicos; Antiinflamatórios não esteroidais; Atypical antipsychotics; Electroanalysis; Electrochemistry; Eletroanalítica; Eletroquímica; Eletroquímica molecular; Molecular electrochemistry; Nonsteroidal anti-inflammatory drugs
• Link de acesso: https://www.teses.usp.br/teses/disponiveis/46/46136/tde-26102022-111633/

In this work, divided in two parts, at first, we studied the chemical interactions of non-steroidal anti-inflammatory drugs (NSAIDs) and their target, the cicloxygenase enzyme, and secondly, the interaction between antipsychotics drugs with the catecholamine neurotransmitters, using electrochemical techniques. To achieve the prior goal, the electrochemical behaviour of dipyrone and its derivatives were studied at glassy carbon electrode, and a oxidation mechanism was proposed. Following, a cicloxygenase enzyme biosensor was developed to evaluate the anti-inflammatory properties and the pharmacological mechanism of the NSAIDs, and the interaction of the enzyme with the most used NSAIDs, dipyrone, acetil-salicylic and salycilic acid, ibuprophen, acetaminophen, and naproxen were evaluated using differential pulse voltammetry technique. The voltammetric results suggest the least and the most effective in inhibit the peroxidase active site are the acetaminophen and the ibuprophen, respectively. Whilst the electrons paramagnetic resonance suggests the enzyme oxygenase active site, are least and the most effective inhibited by the salycilic acid and the dipyrone, respectively. These results confirm the inactivation of the enzyme by a reducer, although the study with the active site and the tyrosyl radical indicate that not only the enzyme can be inactivated by a redox reaction, but also that the NSAIDs perform an allosteric regulation of the enzyme hindering its process, and consequently deactivating the arachidonic cascade. In sequence, the chemical interaction between the highly used antipsychotic drugs olanzapine and quetiapine and the catecholamine neurotransmitters were studied.