Síntese e estudos de modelagem molecular de derivados hidrazinotiazóis potencialmente ativos em doenças negligenciadas
Data
2022-12-14
Autores
Silva, Tassia Leticia da 
Orientadores
Menegon, Renato Farina
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Diversos compostos naturais têm sido testados quanto ao seu uso potencial em Doença de Chagas e Leishmaniose. Destacam-se os derivados de óleos essenciais, principalmente terpenos e derivados fenólicos de baixo peso molecular. Este trabalho tem como objetivo a obtenção de derivados de hidrazinotiazóis e estudos de modelagem molecular. Esses compostos foram obtidos a partir de álcoois alílicos, visando a potencialização de sua atividade leishmanicida. A síntese ocorreu pela oxidação de álcoois alílicos com óxido de manganês. Os aldeídos obtidos foram utilizados para a condensação da tiossemicarbazida e a seguir para a formação da base de Schiff. A tioamina obtida foi condensada com alfa-bromo-nitroacetofenona, pelo mecanismo de Hantszch. O docking reverso foi realizado com a utilização de softwares baseados na web. As reações de oxidação tiveram rendimentos de 60-74% e as reações de formação da base de Schiff tiveram rendimentos de 80-90%. Na última etapa, formando o anel tiazol, o rendimento variou entre 7 e 30%. Estudos de docking reverso têm mostrado como prováveis alvos moleculares em comum entre todos os compostos monoaminoxidase A e enzimas monoaminoxidase B de humanos. Com o uso de uma ferramenta de alinhamento de proteínas, procuramos encontrar alvos semelhantes a alvos humanos em parasitas. Nenhuma enzima semelhante foi encontrada nos parasitas. Os alvos para nossos compostos podem ser exclusivos do parasita, incluindo a membrana celular.
Several natural compounds have been tested for their potential use in Chagas' disease and Leishmaniasis. Of particular note are those derived from essencial oils, mainly terpenes and phenolic derivates of low molecular weight. This work aims to obtain hydrazinotiazoles derivatives and molecular docking studies. These compounds were obtained from allylic alcohols, aiming at the potentialization of their leishmanicidal activity. The synthesis occurred by the oxidation of allylic alcohols with manganese oxide. The aldehydes obtained were used for the condensation of thiosemicarbazide and then formation of the Schiff base. The obtained thioamine was condensed with alpha-bromo-nitroacetophenone, by the Hantszch mechanism. The reverse docking was accomplished with the use of web-based softwares. The oxidation reactions had yields of 60-74% and the formation reactions of the Schiff base had yields of 80-90%. The last step, forming the thiazole ring, the yield ranged between 7 and 30%. Reverse docking studies have shown as likely molecular targets in common among all compounds monoaminoxidase A and monoaminoxidase B enzymes from humans. With the use of a protein alignment tool, we sought to find targets similar to human targets in parasites. No similar enzymes were found in parasites. The targets for our compounds may be unique to the parasite, including the cell membrane.
Several natural compounds have been tested for their potential use in Chagas' disease and Leishmaniasis. Of particular note are those derived from essencial oils, mainly terpenes and phenolic derivates of low molecular weight. This work aims to obtain hydrazinotiazoles derivatives and molecular docking studies. These compounds were obtained from allylic alcohols, aiming at the potentialization of their leishmanicidal activity. The synthesis occurred by the oxidation of allylic alcohols with manganese oxide. The aldehydes obtained were used for the condensation of thiosemicarbazide and then formation of the Schiff base. The obtained thioamine was condensed with alpha-bromo-nitroacetophenone, by the Hantszch mechanism. The reverse docking was accomplished with the use of web-based softwares. The oxidation reactions had yields of 60-74% and the formation reactions of the Schiff base had yields of 80-90%. The last step, forming the thiazole ring, the yield ranged between 7 and 30%. Reverse docking studies have shown as likely molecular targets in common among all compounds monoaminoxidase A and monoaminoxidase B enzymes from humans. With the use of a protein alignment tool, we sought to find targets similar to human targets in parasites. No similar enzymes were found in parasites. The targets for our compounds may be unique to the parasite, including the cell membrane.