Estudo voltamétrico de novos análogos do nitrofural em meio aquoso com potencial atividade antichagásica
Data
2021-01-29
Autores
Almeida, Lígia Scandoglieri de 
Orientadores
La Scalea, Mauro Aquiles
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Sabendo que a quimioterapia atual para a doença de Chagas é tida como ultrapassada e muito tóxica e visando fármacos mais ativos com menos efeitos nocivos para tratamento desta doença, despertase o interesse em compostos nitroheterocíclicos, como o nitrofural (NF), que apresentam esta atividade antichagásica em potencial. A redução eletroquímica destes compostos leva à formação do nitro radical aniônico (RNO2•−) e do derivado hidroxílamínico
(RNHOH), que são considerados os principais responsáveis pela atividade biológica. Compreendendo que as técnicas eletroquímicas são uma excelente alternativa para o estudo de fármacos eletroativos que possuam como característica de sua ação biológica processos de transferência de carga, como no caso destes compostos, o comportamento eletroquímico dos derivados sulfonilhidrazona (NFBS) e nitrofurânico (NTBS), análogos ao NF, foram
estudados por voltametria cíclica, em meio aquoso, utilizando carbono vítreo (ECV) como eletrodo de trabalho. Observouse, em pH 4,0, a formação de um pico catódico irreversível, correspondente à redução do grupo nitro (RNO2) ao derivado hidroxilamínico (RNHOH) com o envolvimento de quatro elétrons (Ecp1 = 0,396 V, NTBS; Ecp1 = 0,355 V, NFBS), sendo que em ambos os casos este pico é deslocado no sentido negativo de potencial com aumento da velocidade de varredura (v). A relação entre Ip1 vs v^1/2 de cada composto se mostrou linear (Ip1 = 2,42 x 10^6– 3,16 x 10^5 ν^1/2, NTBS; Ip1 = 4,48 x 10^6
– 3,85 x 10^5 ν^1/2 NFBS), indicando processo controlado por difusão. Com a variação do pH, Ep1 foi deslocado linearmente nos dois análogos (Ep1 = 0.21 0.045 pH, NTBS; Ep1 = 0.155 0.0532 pH, NFBS) para valores mais negativos de potencial com diminuição da acidez do meio, indicando a existência de etapa de protonação anterior ao processo de transferência de carga. Em meio alcalino, há uma nítida mudança de comportamento em ambos os compostos e, de
forma similar ao nitrofural, observouse a formação do par reversível RNO2/RNO2
•− em pH 12 (Ecp1= 0,577 V e Eap1= 0,468 V, NTBS; Ecp1= 0,553 V e Eap1= 0,460 V, NFBS).
Knowing that the current chemotherapy for Chagas disease is considered to be outdated and very toxic and targeting more active drugs with fewer harmful effects for the treatment of this disease, interest is aroused in nitroheterocyclic compounds, such as nitrofural (NF), which present this potential antichagasic activity. The electrochemical reduction of these compounds leads to the formation of nitro anion radical (RNO2•−) and hydroxyminic derivative (RNHOH), which are considered the main responsible for biological activity. Understanding that electrochemical techniques are an excellent alternative for the study of electroactive drugs that have as characteristic of their biological action load transfer processes, as in the case of these compounds, the electrochemical behavior of sulfonyl hydrazone (NFBS) and nitrofuranic (NTBS) derivatives, analogous to NF, were studied by cyclic voltammetry, in aqueous medium, using glassy carbon eletrode (ECV) as a working electrode. At pH 4.0, the formation of an irreversible cathodic peak was observed, corresponding to the reduction of the nitro group (RNO2) to the hydroxylamine derivative (RNHOH) with the involvement of four electrons (Ecp1 = 0.396 V, NTBS; Ecp1 = 0.355 V, NFBS), and in both cases this peak is moved in the negative direction of potential with increased scanning speed (v). The relationship between Ip1 vs v^1/2 of each compound was linear (Ip1 = 2.42 x 10^6 - 3.16 x 10^5 v^1/2, NTBS; Ip1 = 4.48 x 10^6 - 3.85 x 10^5v^1/2, NFBS), indicating diffusion controlled process. With the pH variation, Ep1 was linearly displaced in the two analogues (Ep1 = 0.21 0.045 pH, NTBS; Ep1 = 0.155 0.0532 pH, NFBS) for more negative potential values with decreased acidity of the medium, indicating the existence of protonation stage prior to the load transfer process. In alkaline medium, there is a clear change in behavior in both compounds and, similarly to NF, the formation of the reversible pair RNO2/RNO2•− was observed at pH 12 (Ecp1= 0,577 V e Eap1= 0,468 V, NTBS; Ecp1= 0,553 V e Eap1= 0,460 V, NFBS).
Knowing that the current chemotherapy for Chagas disease is considered to be outdated and very toxic and targeting more active drugs with fewer harmful effects for the treatment of this disease, interest is aroused in nitroheterocyclic compounds, such as nitrofural (NF), which present this potential antichagasic activity. The electrochemical reduction of these compounds leads to the formation of nitro anion radical (RNO2•−) and hydroxyminic derivative (RNHOH), which are considered the main responsible for biological activity. Understanding that electrochemical techniques are an excellent alternative for the study of electroactive drugs that have as characteristic of their biological action load transfer processes, as in the case of these compounds, the electrochemical behavior of sulfonyl hydrazone (NFBS) and nitrofuranic (NTBS) derivatives, analogous to NF, were studied by cyclic voltammetry, in aqueous medium, using glassy carbon eletrode (ECV) as a working electrode. At pH 4.0, the formation of an irreversible cathodic peak was observed, corresponding to the reduction of the nitro group (RNO2) to the hydroxylamine derivative (RNHOH) with the involvement of four electrons (Ecp1 = 0.396 V, NTBS; Ecp1 = 0.355 V, NFBS), and in both cases this peak is moved in the negative direction of potential with increased scanning speed (v). The relationship between Ip1 vs v^1/2 of each compound was linear (Ip1 = 2.42 x 10^6 - 3.16 x 10^5 v^1/2, NTBS; Ip1 = 4.48 x 10^6 - 3.85 x 10^5v^1/2, NFBS), indicating diffusion controlled process. With the pH variation, Ep1 was linearly displaced in the two analogues (Ep1 = 0.21 0.045 pH, NTBS; Ep1 = 0.155 0.0532 pH, NFBS) for more negative potential values with decreased acidity of the medium, indicating the existence of protonation stage prior to the load transfer process. In alkaline medium, there is a clear change in behavior in both compounds and, similarly to NF, the formation of the reversible pair RNO2/RNO2•− was observed at pH 12 (Ecp1= 0,577 V e Eap1= 0,468 V, NTBS; Ecp1= 0,553 V e Eap1= 0,460 V, NFBS).