کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10582653 | 981075 | 2012 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Structural modifications modulate stability of glutathione-activated arylated diazeniumdiolate prodrugs
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
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چکیده انگلیسی
JS-K, a diazeniumdiolate-based nitric oxide (NO)-releasing prodrug, is currently in late pre-clinical development as an anti-cancer drug candidate. This prodrug was designed to be activated by glutathione (GSH) to release NO. To increase the potency of JS-K, we are investigating the effect of slowing the reaction of the prodrugs with GSH. Herein, we report the effect of replacement of nitro group(s) by other electron-withdrawing group(s) in JS-K and its homo-piperazine analogues on GSH activation and the drugs' biological activity. We show that nitro-to-cyano substitution increases the half-life of the prodrug in the presence of GSH without compromising the compound's in vivo antitumor activity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 20, Issue 9, 1 May 2012, Pages 3094-3099
Journal: Bioorganic & Medicinal Chemistry - Volume 20, Issue 9, 1 May 2012, Pages 3094-3099
نویسندگان
Rahul S. Nandurdikar, Anna E. Maciag, Ryan J. Holland, Zhao Cao, Paul J. Shami, Lucy M. Anderson, Larry K. Keefer, Joseph E. Saavedra,