کد مقاله کد نشریه سال انتشار مقاله انگلیسی ترجمه فارسی نسخه تمام متن
10533131 961849 2005 8 صفحه PDF سفارش دهید دانلود رایگان
عنوان انگلیسی مقاله ISI
Comparative binding of antitumor indazolium [trans-tetrachlorobis(1H-indazole)ruthenate(III)] to serum transport proteins assayed by capillary zone electrophoresis
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موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Comparative binding of antitumor indazolium [trans-tetrachlorobis(1H-indazole)ruthenate(III)] to serum transport proteins assayed by capillary zone electrophoresis
چکیده انگلیسی
The indazolium [trans-tetrachlorobis(1H-indazole)ruthenate(III)] coordination compound shows notable antiproliferative activity in different tumor models and has recently ended phase I clinical trials as a lead anticancer metallodrug candidate. Its approval could be greatly facilitated if more precise information was available on the rate and degree of the drug's transformation occurring upon interaction with serum transport proteins and on the stability of the adducts formed. With this objective, a new method has been developed for the determination of the protein-binding rate and association constants under simulated physiological conditions by capillary zone electrophoresis (CZE). These binding parameters were assessed by monitoring the time- and concentration-dependent changes in peak area responses of reaction components, constructing the corresponding binding curves, and conducting a mathematical analysis. Comparison of the apparent rate constants determined by CZE revealed that indazolium [trans-tetrachlorobis(1H-indazole)ruthenate(III)] binds to transferrin much faster than to albumin: k = 39.5 × 10−4 and 3.3 × 10−4 s−1, respectively. The corresponding association constants are indicative of moderate metal-protein coordination, with a somewhat higher affinity of the Ru complex toward albumin (9910 and 6460 M−1, respectively). The results of our study confirm in a quantitative manner that, in real bloodstream circumstances, plasma albumin may serve as a reservoir and a natural carrier of the administered ruthenium drug and hence mediate its accumulation in tumors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Analytical Biochemistry - Volume 341, Issue 2, 15 June 2005, Pages 326-333
نویسندگان
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