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Current Topics in Pharmacology   Volumes    Volume 19 
Voltammetric detection and quantification of pentacyano(isoniazid)ferrate(II), a metal-based drug candidate for the treatment of tuberculosis
Adilio da S. Dadda, Valnês S. Rodrigues-Junior, Mariane Rotta, Leonardo K. B. Martinelli, Maria M. Campos, Eduardo H. S. Sousa, Antônio F. M. Pinto, Pablo Machado, Luiz A. Basso, Diógenes S. Santos
Pages: 75 - 86
Number of pages: 12
Current Topics in Pharmacology
Volume 19 

Copyright © 2015 Research Trends. All rights reserved

A voltammetric method was employed to detect and quantify pentacyano(isoniazid)ferrate(II) compound (IQG-607), which is an inorganic complex with anti-tuberculosis (TB) activity. The technique used was adsorptive stripping voltammetry (AdSV) and application of a differential pulse scan in the stripping step (DPAdSV). The McIlvaine buffer was used as the base electrolyte. The compound presented three peaks at -0.70 V, -0.95 V and -1.1 V. Optimization of the method to improve the peak current was carried out by varying different factors such as pulse amplitude, pulse time, deposition time, deposition potential, and pH of the base electrolyte. The calibration curve was linear for IQG-607 concentrations ranging from 1 to 20 µg mL-1, and the limit of detection (LOD) and limit of quantification (LOQ) were 0.5 µg mL-1 and 1 µg mL-1, respectively. The stability of IQG-607 stock solution at two temperatures was investigated by the DPAdSV method, and concomitant M. tuberculosis 2-trans-enoyl-ACP(CoA) reductase (MtInhA) enzyme activity measurements were carried out. These results suggest the formation of isonicotinic acid (INA) at -1.2 V as the degradation product, and revealed that the compound is stable for at least 1 week at 4 ºC in solution. In addition, the correlation between reduction in the value of the first-order rate constant of MtInhA enzyme inhibition and IQG-607 chemical stability provides evidence that the latter, and not its metabolite(s), is the active chemical compound. The optimization of experimental conditions to detect and quantify the IQG-607 compound by the DPAdSV method represents an experimental approach on which to base further pharmacokinetic studies in complex biological fluids, before embarking on costly clinical assays. The IQG-607 compound may be an example of a promising metal-based antimicrobial that inhibits the activity of a validated and druggable target (MtInhA) aiming at the development of an anti-TB agent.
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