Síntese de novos análogos isoxazólicos derivados das neolignanas veraguensina, grandisina e machilina G com potencial atividade contra leishmanioses

• Autor(a) principal: Pereira, Luiz Fernando Polizelli
• Data de Publicação: 2023
• Tipo de documento: Trabalho de conclusão de curso
• Idioma: por
• Título da fonte: Repositório Institucional da UFMS
• Texto Completo: https://repositorio.ufms.br/handle/123456789/5941
• topic: Leishmaniose; Neolignanas; Isoxazóis; Cicloadição; Relação Estrutura-Atividade; Desenho de Fármacos

Neglected diseases are a set of endemic diseases in low-income regions where investments in treatment, diagnosis and control are negligible, since the affected population is less financially well-off. Leishmaniasis is a zoonosis characterized by extensive lesions on the skin and mucous membranes that do not regress without treatment. The recommended treatments are expensive and/or difficult to administer, in addition to having numerous toxic effects. In view of this, it is necessary to search for new alternatives for the treatment of this disease and a great source of active structures are natural products. However, substances from plants, such as neolignans, can cause undesirable effects, and therefore the chemical improvement of these molecules is an excellent tool in the search for increasingly potent and selective drugs. The bioisosterism strategy is a chemical improvement technique widely used in medicinal chemistry that has already proven efficient in the search for substances against leishmaniasis. Another technique is the addition of halogen groups in the structure as a possibility to increase the action of the molecule against the protozoan forms. The main synthesis was based on the Huisgen cycloaddition reaction or dipolar [1+3] cycloaddition, between chlorooximes and terminal acetylenes, for the formation of chlorinated isoxazole analogues of neolignans and their respective positional isomers. The antileishmanial activity was tested and the data were compared to grandisin and amphotericin B and tabulated. A comparison study between pharmacological and structural parameters was also carried out and the conclusion was that the structural parameters had greater relevance in the biological activity in this case.