Quinoxaline 1,4-di-N-oxide Derivatives: Interest in the Treatment of Chagas Disease

Abstract

Resumo: Mais de 100 milhões de pessoas estão em risco de contrair a doença de Chagas. Estima-se que em 2008, mais de 10.000 pessoas morreram devido a esta patologia. Apesar de a doença ter sido descoberta há mais de 100 anos, ainda é preciso encontrar tratamento seguro e eficaz. Portanto, novos fármacos eficazes contra a doença de Chagas necessitam urgentemente serem descobertos. Derivados de quinoxalina apresentam interessantes propriedades biológicas (anti-infecciosa, citotóxica, anti-candida, anti-protozoário) e a avaliação de suas propriedades farmacológicas ainda está em andamento. Com respeito a isso, nós estamos há mais de uma década em busca de agentes anti-chagásicos. Nesta revisão mostramos nosso trabalho em andamento para identificação de novos agentes anti-T. cruzi com o padrão estrutural quinoxalina-di-N-óxido e apresentamos a relação estrutura-atividade observada entre as diferentes substituições nas posições C-2, C-3, C-6 e C-7 do anel da quinoxalina.Palavras-chave: Doença de Chagas; Trypanosoma cruzi; 1,4-di-N-óxido Quinoxalinas. AbstractsMore than 100 million people are at risk of contracting Chagas disease. It is estimated that in 2008, Chagas disease was responsible for the death of more than 10,000 people. Despite the fact that there are more than 100 years since the disease was discovered, safe and effective treatments still have to be found. Therefore, new drugs active against Chagas disease are urgently required. Quinoxaline derivatives show very interesting biological properties (antiinfective, cytotoxic, anticandida, antiprotozoal) and evaluation of their medicinal chemistry is still in progress. In this regard, we have spent more than a decade in the search for antiChagasic agents. In this review, we summarize our on-going work to identify new anti-T. cruzi agents with the quinoxaline-di-N-oxide scaffold. We present the structure-activity relationship observed among the different substitutions in C-2, C-3, C-6 and C-7 position of the quinoxaline ring.

Stimulation of Sulfonamides Antibacterial Drugs Activity as a Result of Complexation with Ru(III): Physicochemical and Biological Study

“…Knowledge of the redox properties of pharmaceuticals is also of use in studies focusing on developing new methods that allow electrochemically controlled drug release [60]. Moreover, it has been shown that the mechanism of the biological activity of some compounds is influenced by their redox activity [61,62]. Reliable and accurate correlations between the electrochemical properties and the biological activity of pharmaceuticals are still being sought.…”

Voltammetric Study of Some 3-Aryl-quinoxaline-2-carbonitrile 1,4-di-N-oxide Derivatives with Anti-Tumor Activities

“…One important feature for their biological activities is the presence of both N -oxide functional groups in the pyrazine ring of the basic quinoxaline structure. N -oxidation generally enhances the scope and level of their biological properties [ 1 , 2 , 16 ], and may be important for bioreduction [ 10 ]. It is well-known that some quinoxaline 1,4-di- N -oxide derivatives undergo bioreduction under hypoxic conditions, leading to the formation of a radical capable of cleaving DNA [ 2 , 3 ].…”

Photosensitive and pH-dependent activity of pyrazine-functionalized carbazole derivative as promising antifungal and imaging agent

“…Electrochemistry of carbazole compounds is an object of interest mainly because of their applications [19][20][21][22][23] . However, it has been shown that the mechanism of biological action of some biologically active compounds is associated with their redox activity 24,25 . The aforementioned comparisons were expected to lead to solving research problems.…”