کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9002287 | 1118581 | 2005 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Antioxidant, prooxidant and cytotoxic activity of hydroxylated resveratrol analogues: structure-activity relationship
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کلمات کلیدی
HydroxystilbeneDMPOCOXESRDPPHPARPDTPALPO2,2-diphenyl-1-picrylhydrazyl - 2،2-دی فینیل-1-پریکیل هیدرازیل5,5-dimethyl-1-pyrroline-N-oxide - 5،5-دی متیل-1-پیرولین-N-اکسیدO2− - O2-ROS - ROSAntioxidants - آنتی اکسیدانcyclooxygenase - آنزیم سیکلواکسیژنازDiethylenetriaminepentaacetic acid - دی اتیلنتریمین پنتا اسیدهای اسیدsuperoxide radical - رادیکال سوپراکسیدPhenoxyl radical - رادیکال فنوکسیلElectron spin resonance - رزونانس اسپین الکترونResveratrol - رسوراترولSOD - سدHL-60 cells - سلول های HL-60Cytotoxicity - سمیت سلولیSuperoxide dismutase - سوکسوکس دیسموتازHydroxystilbenes - هیدروکسیستیبلنLipid peroxidation - پراکسیداسیون لیپیدProoxidants - پروکسیدین هاPoly(ADP-ribose) polymerase - پلیمر (ADP-ribose) پلیمرازReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Resveratrol (trans-3,4â²,5-trihydroxystilbene), a naturally occurring hydroxystilbene, is considered an essential antioxidative constituent of red wine possessing chemopreventive properties. However, resveratrol and even more its metabolite piceatannol were reported to have also cytostatic activities. In order to find out whether this is related to antioxidative properties of those compounds, we synthesized five other polyhydroxylated resveratrol analogues and studied structure-activity relationships between pro-/antioxidant properties and cytotoxicity. Radical scavenging experiments with O2â (5,5-dimethyl-1-pyrroline-N-oxide/electron spin resonance (DMPO/ESR)) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) (photometry) revealed that 3,3â²,4â²,5-tetrahydroxystilbene (IC50: 2.69 μM; k9: 443000 Mâ1 sâ1), 3,4,4â²,5-tetrahydroxystilbene (IC50: 41.5 μM; k9: 882000 Mâ1 sâ1) and 3,3â²,4,4â²,5,5â²-hexahydroxystilbene (IC50: 5.02 μM), exerted a more than 6600-fold higher antiradical activity than resveratrol and its two other analogues. Furthermore, in HL-60 leukemic cells hydroxystilbenes with ortho-hydroxyl groups exhibited a more than three-fold higher cytostatic activity compared to hydroxystilbenes with other substitution patterns. Oxidation of ortho-hydroxystilbenes in a microsomal model system resulted in the existence of ortho-semiquinones, which were observed by ESR spectroscopy. Further experiments revealed that these intermediates undergo redox-cycling thereby consuming additional oxygen and forming cytotoxic oxygen radicals. In contrast to compounds with other substitution patterns hydroxystilbenes with one or two resorcinol groups (compounds 1 and 3) did not show an additional oxygen consumption or semiquinone formation. These findings suggest that the increased cytotoxicity of ortho-hydroxystilbenes is related to the presence of ortho-semiquinones formed during metabolism or autoxidation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 69, Issue 6, 15 March 2005, Pages 903-912
Journal: Biochemical Pharmacology - Volume 69, Issue 6, 15 March 2005, Pages 903-912
نویسندگان
Marek Murias, Walter Jäger, Norbert Handler, Thomas Erker, Zsuzsanna Horvath, Thomas Szekeres, Hans Nohl, Lars Gille,