کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10574926 | 976680 | 2005 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Electron transfer kinetics and mechanistic study of the thionicotinamide coordinated to the pentacyanoferrate(III)/(II) complexes: a model system for the in vitro activation of thioamides anti-tuberculosis drugs
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی معدنی
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چکیده انگلیسی
The mechanism of activation thioamide-pyridine anti-tuberculosis prodrugs is poorly described in the literature. It has recently been shown that ethionamide, an important component of second-line therapy for the treatment of multi-drug-resistant tuberculosis, is activated through an enzymatic electron transfer (ET) reaction. In an attempt to shed light on the activation of thioamide drugs, we have mimicked a redox process involving the thionicotinamide (thio) ligand, investigating its reactivity through coordination to the redox reversible [FeIII/II(CN)5(H2O)]2â/3â metal center. The reaction of the FeIII complex with thionicotinamide leads to the ligand conversion to the 3-cyanopyridine species coordinated to a FeII metal center. The rate constant, ket = 10 sâ1, was determined for this intra-molecular ET reaction. A kinetic study for the cross-reaction of thionicotinamide and [Fe(CN)6]3â was also carried out. The oxidation of thionicotinamide by [Fe(CN)6]3â leads to formation of mainly 3-cyanopyridine and [Fe(CN)6]4â with a ket = (5.38 ± 0.03) Mâ1 sâ1 at 25 °C, pH 12.0. The rate of this reaction is strongly dependent on pH due to an acid-base equilibrium related to the deprotonation of the R-SH functional group of the imidothiol form of thionicotinamide. The kinetic results reinforced the assignment of an intra-molecular mechanism for the ET reaction of [FeIII(CN)5(H2O)]2â and the thioamide ligand. These results can be valuable for the design of new thiocarbonyl-containing drugs against resistant strains of Mycobacterium tuberculosis by a self-activating mechanism.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Inorganic Biochemistry - Volume 99, Issue 2, February 2005, Pages 368-375
Journal: Journal of Inorganic Biochemistry - Volume 99, Issue 2, February 2005, Pages 368-375
نویسندگان
Eduardo H.S. Sousa, Daniel L. Pontes, Izaura C.N. Diógenes, Luiz G.F. Lopes, Jaim S. Oliveira, Luiz A. Basso, Diógenes S. Santos, Ícaro S. Moreira,