Navegando por Assunto "Molecular modification"

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Planejamento, Síntese, Avaliação das Propriedades Teóricas de orto-Regioisômeros Substituídos do Paracetamol
(Universidade Federal do Pará, 2018-12-28) MORAIS, Roberto Barbosa de; BORGES, Rosivaldo dos Santos; http://lattes.cnpq.br/4783661132100859; https://orcid.org/0000-0003-4072-7573
Paracetamol is a clinically proven analgesic and antipyretic, which promotes analgesia by elevating the pain threshold and antipyretic through action in the hypothalamic center that regulates the temperature. Currently paracetamol is one of the medicines that is available in all the countries of the world in places related to health and can be acquired without prescription. Considered one of the most widely used drugs in the world as it is cheap and easy to access, it can also be used from birth to the elderly. Like non-steroidal anti-inflammatory drugs (NSAIDs) paracetamol is able to inhibit the synthesis of prostaglandins from arachidonic acid under specific conditions by inhibiting cyclooxygenase (COX). Although it is considered safe at therapeutic doses, Paracetamol has a toxicity attributed to one of its metabolic intermediates called N-acetyl-p-imine-benzoquinone (NAPQI), produced through enzymes present in cytochrome P450 (CYPE21). Thus, the objective of this present work is to plan, synthesize and evaluate possible antinociceptive and antipyretic activities of paracetamol analogues, ortacetamol and its derivatives in order to obtain a less toxic derivative. The calculations of electronic properties such as higher energy occupied molecular orbital (HOMO), lower energy unoccupied molecular orbital (LUMO), ionization potential (PI), phenolic bond dissociation energy (BDEOH) and spin densities were performed using the Gaussview and Gaussian 2009 packages. The values of the average values of BDENH, among others, are those that are observed with the quality of a heating cycle for the high speed with the possibility of a chelation defined by a hydrogen bond of the amide with the phenoxyl radical. Given the results it is possible that BDENH energy compounds may be less potent than hindering the action of CYP on oxidation to form toxic intermediates. A proposed chlorinated derivative was proposed and synthesized. It is in biological evaluation phase. Orthacetamol was more potent antioxidant than paracetamol. Experimental results are in aggrement with theoretical values. We conclude that ortcetamol may be a potentially safer bioactive candidate than paracetamol.