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Previous issue date: 2015-07-10 / Tuberculosis (TB) caused predominantly by Mycobacterium tuberculosis is an infectious disease responsible for a significantly number of deaths worldwide. The first line TB drugs that are currently used, and others available, present several problems, such as duration and complexity of treatment, and adverse effects, factors that decrease the patient adherence to treatment regimen. These problems increase the number of cases of drug resistant TB. The pentacyano(isoniazid)ferrate(II) (IQG-607) compound is an inorganic complex designed to treat INH-resistant strains of M. tuberculosis containing mutations in catalase-peroxidase gene, katG. The compound appears to be a promising anti-TB drug candidate according to previous studies that demonstrated its effectiveness both in vitro and in vivo. However, the difficulties encountered in the development of an analytical method for detection and quantification of the compound, due to its chemical properties, were impeding further studies, such as the pharmacokinetic studies. In this context, the present study describes two analytical methods for the detection of IQG-607 for the first time. The voltammetric method was shown to be a powerful analytical tool for quantification of IQG-607 and may be used to monitoring the stability and quality control. The proposed method, together with enzymatic inhibition assay, shown that the IQG-607 is stable for at least 1week at 4 ?C. The detection of IQG-607 by high performance liquid chromatography (HPLC) was also described, and we were able to observe the retention of the compound on the stationary phase of a chromatography column for the first time in this work. In addition, the analysis of IQG-607 in mouse plasma by HPLC was also demonstrated. Therefore, this conventional method will be optimized and validated to conduct pharmacokinetics studies. / A tuberculose (TB) causada predominantemente por Mycobacterium tuberculosis ? uma doen?a infecciosa respons?vel por um n?mero consider?vel de mortes em todo o mundo. Os medicamentos utilizados no tratamento de primeira linha atual, e os demais dispon?veis, apresentam diversos problemas, como a dura??o, complexidade, e efeitos adversos, dificultando a ades?o dos pacientes ao regime terap?utico. Isto favorece o aumento do n?mero de casos de TB resistente a medicamentos. O pentaciano(isoniazida)ferrato(II) (IQG-607) ? um composto proposto para agir contra casos de TB resistentes ? INH devido a infec??o com cepas que possuem muta??es no gene katG. O composto demonstrou ser um promissor agente anti-TB em estudos pr?vios, e a sua efic?cia in vitro e in vivo foi comprovada. No entanto, as dificuldades encontradas no desenvolvimento de um m?todo anal?tico para a detec??o e quantifica??o do composto devido as suas caracter?sticas qu?micas estavam impedindo a realiza??o de outros estudos, e dentre eles, a determina??o de par?metros farmacocin?ticos. Tendo isto em vista, o presente trabalho descreve, pela primeira vez, dois m?todos anal?ticos para detec??o de IQG-607. O m?todo voltam?trico mostrou potencialidade na quantifica??o do composto, podendo ser utilizado para monitorar a estabilidade e em controle de qualidade. Observamos, por meio deste m?todo, juntamente com ensaios de inibi??o enzim?tica, que o IQG-607 ? est?vel em solu??o por at? 1 semana se for mantido a 4?C. A detec??o do IQG-607 por cromatografia l?quida de alta efici?ncia (CLAE) tamb?m foi demonstrada, e, pela primeira vez, observamos a intera??o do composto em coluna cromatogr?fica. Ainda, por CLAE, demonstramos a detec??o do IQG-607 no plasma de camundongos, e por ser um m?todo convencional, ser? otimizado e validado para a realiza??o de futuros estudos de farmacocin?tica.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/6323 |
| Date | 10 July 2015 |
| Creators | Dadda, Adilio da Silva |
| Contributors | Basso, Luiz Augusto, Rodrigues Junior, Valn?s da Silva |
| Publisher | Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Programa de P?s-Gradua??o em Biologia Celular e Molecular, PUCRS, Brasil, Faculdade de Bioci?ncias |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 8198246930096637360, 600, 600, 600, 36528317262667714, -3439178843068202161 |
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