کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485815 | 1114367 | 2011 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
In vitro Conversion of Model Sulfenamide Prodrugs in the Presence of Small Molecule Thiols
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Sulfenamide prodrugs of amide and urea functional group containing drugs have recently been proposed as a means of altering the physical and bioproperties of problematic drug molecules containing these two functionalities. Sulfenamides have been shown to revert to the parent drug via reaction with thiols. Explored here is the mechanism for this reaction. The stoichiometry and pH dependency of the in vitro reversion of two model prodrugs of the oxazolidinone, linezolid, and a sulfenamide of phthalimide were studied at 25°C in the presence of thiols, including cysteine and glutathione, of varying basicity. High-performance/pressure liquid chromatography and liquid chromatography-mass spectrometry results showed the near quantitative reversion of the sulfenamides to the parent drug with simultaneous formation of a mixed disulfide. The pH and the dependency of the reaction on the basicity of the thiol strongly supported the role of the thiolate specie in the conversion. The reaction is consistent with an SN2 type mechanism seen in the reaction of some thiols with disulfides.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 3, March 2011, Pages 1001-1008
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 3, March 2011, Pages 1001-1008
نویسندگان
Kwame W. Nti-Addae, Valentino J. Stella,