کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2603780 | 1133835 | 2007 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Comparison of the nucleic acid covalent binding capacity of two nitro-substituted benzazolo[3,2-a]quinolinium salts upon enzymatic reduction
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کلمات کلیدی
CIDESI-MSDNA adductsXanthine oxidase - زانتین اکسیداز2′-deoxyguanosine - 2'-deoxyguanosineCollision-induced dissociation - اختلاف ناشی از برخوردElectrospray Ionization Mass Spectrometry - اسپکترومتر جرم یونیزاسیون ElectrosprayBioreductive drugs - داروهای بیولوژیکMass spectrometry - طیف سنجی جرمیhypoxanthine - هیپوکسانتینHypoxia - هیپوکسی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The DNA binding capacity of two nitro-substituted benzazolo[3,2-a]quinolinium chlorides (NBQs), NBQ-38 and NBQ-95, was evaluated upon their enzymatic reduction with hypoxanthine (HX)/xanthine oxidase (XO) under anaerobic conditions. In the presence of 2â²-deoxyguanosine (2â²-dG) or calf thymus DNA, covalent-addition products were monitored. Reactions of each NBQ with 2â²-dG or DNA differed in the NBQ to HX molar ratio. Control reactions, one without HX/OX and another under aerobic conditions, were also analyzed. Adducts were isolated and characterized by high performance liquid chromatography (HPLC) and electrospray ionization-mass spectrometry (ESI-MS). Authentic samples of the reduced forms of these NBQs, identified as ABQ-38 and ABQ-95, were synthesized as standards to monitor bioreduction processes. HPLC analysis showed that the yield of formation of an unknown product (possibly, 2â²-dG-NHBQ-38 adduct) from the reaction of NBQ-38 with 2â²-dG and DNA was proportional to the HX to NBQ-38 molar ratio. ESI-MS analysis of the DNA hydrolysates showed evidence of an adduct formed upon bioreduction of NBQ-38 by the ions detection at m/z 528.3 and 454.8, consistent with chemical structures of a 2â²-dG-NHBQ-38 adduct and a fragment ion. DNA adducts were not observed with NBQ-95, although the corresponding bioreduction product ABQ-95 was detected by ESI-MS. This study provides mechanistic information of these bioreductively-activated pro-drugs with potential therapeutic applications.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology in Vitro - Volume 21, Issue 6, September 2007, Pages 1155-1164
Journal: Toxicology in Vitro - Volume 21, Issue 6, September 2007, Pages 1155-1164
نویسندگان
Beatriz Zayas, Juan Beyley, Maria Terron, Marisol Cordero, Wigberto Hernandez, Antonio E. AlegrÃa, Osvaldo Cox,