Novos nitratos orgânicos derivados de biomassas como potenciais fármacos cardiovasculares

• Ano de defesa: 2017
• Autor(a) principal: Brandão, Maria Cláudia Rodrigues
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal da Paraíba; Brasil; Química; Programa de Pós-Graduação em Química; UFPB
• Palavras-chave em Português: Nitratos orgânicos; Doadores de óxido nítrico; Vasodilatadores; Organic nitrates; Oxide nitric donors; Vasodilator; CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
• Link de acesso: https://repositorio.ufpb.br/jspui/handle/123456789/13081

Cardiovascular diseases are the leading cause of death in the world, killing about 17 million people a year, according to the World Health Organization. The main means of treating these diseases is by controlling the levels of endogenous nitric oxide, whose regulation Depends on the administration of chemical species donor of this oxide. The purpose of this study was to develop new formulations of organic nitrates with potential to act as a pro-drug, starting from low-cost raw material, mainly biofuels co-products and biomass reuse. Seventeen organic nitrates were synthesized, thirteen of them being unpublished molecules, all obtained in excellent yields and satisfactorily characterized by 1H NMR, 13C NMR and IV spectroscopy. To this end, in addition to commercially available reagents, was used crude glycerine obtained from the production of biodiesel, previously treated and purified, higher alcohols distillate of the fusel oil, which is a by-product of ethanol production, and furfural which is a derivative of lignocellulose. These compounds were synthesized from the nitration of alcohols and alkoxy ethers by reaction with nitric acid, and chloro esters by reaction with silver nitrate. The in silico studies indicate that these molecules present excellent potential for drugs, presenting low toxicity, and taking into account the physicochemical parameters that are determinant in the absorption, distribution, metabolism and excretion of a drug. All tests of cardiovascular activity performed were satisfactory, demonstrating that the synthesized nitrates have a vasorelaxant potential equal to or greater than the reference compounds, with the advantage of not provoking oxidative stress and consequent tolerance to the drug. In general, it was verified that the proposed changes in the carbon skeleton of the new nitrates developed brought advantages of application to the compounds, with an increase in their beneficial effects attributed also to the increase of the carbon chain.