کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10585429 | 981366 | 2012 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Reactive metabolites of desipramine and clomipramine: The kinetics of formation and reactivity with DNA
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کلمات کلیدی
HRPTCAsPCIROS - ROSDNA damage - آسیبDNAOne-electron oxidation - اکسیداسیون یک الکترونEPR - تشدید پارامغناطیس الکترونElectron paramagnetic resonance - تشدید پارامغناطیس الکترونtricyclic antidepressants - داروهای ضد افسردگی سه حلقه ایMichaelis–Menten kinetics - سینتیک Michaelis-MentenRate constants - نرخ ثابتHorseradish peroxidase - پراکسیداز هوررادیشReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Tricyclic antidepressants (TCAs), along with phenothyazines and some industrial chemicals, are shown to react with enzymes that exhibit peroxidase activity. These reactions result in the formation of reactive intermediates having unpaired electrons. The peroxidase oxidation and reactivity of two TCAs, desipramine and clomipramine, were investigated. As a model of peroxidase, horseradish peroxidase (HRP) was employed. The products of the peroxidase catalyzed oxidation of desipramine and clomipramine were identified as N-dealkylated compounds iminodibenzyl and 3-chloroiminodibenzyl using the GC/MS technique. Both drugs formed broad UV/vis absorption spectra in the presence of HRP and H2O2, indicating the formation of a radical cations-reactive intermediate of the oxidation reaction. The dynamics of the formation of the desipramine intermediate was studied using UV/vis spectroscopy. The extinction coefficient was measured for the reactive intermediate, 7.80Â ÃÂ 103Â Mâ1Â cmâ1, as well as the apparent Michaelis-Menten and catalytic constants, 4.4Â mM and 2.3Â sâ1, respectively. Both desipramine and clomipramine degraded DNA in the presence of HRP/H2O2, as was revealed by agarose gel electrophoresis and PCI extraction. Manipulating the kinetic parameters of drug's radical formation and determining the extent of degradation to biomolecules could be potentially used for designing effective agents exhibiting specific reactivity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 20, Issue 1, 1 January 2012, Pages 340-345
Journal: Bioorganic & Medicinal Chemistry - Volume 20, Issue 1, 1 January 2012, Pages 340-345
نویسندگان
Ekaterina A. Korobkova, John Nemeth, Mikeisha Cadougan, Abhishek Venkatratnam, Mohanram Bassit, Nikolay Azar,