Síntese de derivados benzofuroxânicos com atividade anti-Mycobacterium tuberculosis

• Autor(a) principal: Romano, Priscilla
• Data de Publicação: 2021
• Tipo de documento: Trabalho de conclusão de curso
• Idioma: por
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://hdl.handle.net/11449/215668
• topic: Mycobacterium tuberculosis; Tuberculose; Benzofuroxano; Resistência aos fármacos; Síntese; Tratamento

Tuberculosis is an infectious disease caused by etiological agents from seven species that are part of the Mycobacterium tuberculosis (Mtb) complex, with Mtb being the most commonly found. High mortality rates are still found, mainly in developing countries. In 2019, the number of deaths reached 1.4 million, making it the biggest cause of deaths from infectious diseases in the world. Furthermore, the emergence of drug-resistant strains has increased the challenge to control the disease. The development of new drugs is one of the strategies that must be pursued to ensure greater control of the disease. Previous results from the research group Lapdesf have identified benzofuroxan (GF5) compounds as important anti-Mtb prototypes. Despite the promising effects, the low water solubility demands chemical structure modification strategies. In this course completion work, compounds (6a,9a) were planned and compound 6a (6-((3-fluoro-4-thiomorpholinophenyl) carbamoyl)benzo[c][1,2,5]oxadiazole 1-oxy was synthesized. ), an unprecedented molecule, exploring the classic bioisoterism strategy in the heterocyclic ring of benzofuroxane, substituting a carbon for a nitrogen, which was obtained with yields of 25%. The starch intermediates that make up the planned compounds had yields ranging from 60 to 54%. The product 6a (6-((3-fluoro-4- thiomorpholinophenyl)carbamoyl)benzo[c][1,2,5]oxadiazole 1-oxy) obtained from the coupling reaction was obtained with 23%. Computational data showed that compounds 6a,9a compounds have greater water solubility and modification of pharmacokinetic parameters. The search for new benzofuroxane derivatives with greater water solubility was obtained through the biosisosterism strategy, which may constitute a new alternative for the search for anti-Mtb drugs.