Ruthenium-containing P450 inhibitors for dual enzyme inhibition and DNA damage

2017 ◽  
Vol 46 (7) ◽  
pp. 2165-2173 ◽  
Author(s):  
Ana Zamora ◽  
Catherine A. Denning ◽  
David K. Heidary ◽  
Erin Wachter ◽  
Leona A. Nease ◽  
...  
Keyword(s):  
Dna Damage ◽  
Drug Resistance ◽  
Cytochrome P450 ◽  
Enzyme Inhibition ◽  
Metal Center ◽  
P450 Inhibitors

A light-activated prodrug delivers both a DNA damaging metal center and a cytochrome P450 inhibitor to prevent drug resistance.

scholarly journals Evaluation of the Protective Effects of Quercetin, Rutin, Naringenin, Resveratrol and Trolox Against Idarubicin-Induced DNA Damage

2010 ◽  
Vol 13 (2) ◽  
pp. 231 ◽  
Author(s):  
Haydar Çelik ◽  
Emel Arinç
Keyword(s):  
Dna Damage ◽  
Cytochrome P450 ◽  
Mitomycin C ◽  
Dna Strand Breaks ◽  
Protective Effects ◽  
Cytochrome P450 Reductase ◽  
Strand Breaks ◽  
P450 Reductase ◽  
Nadph Cytochrome P450 Reductase ◽  
Dna Strand

PURPOSE. Idarubicin is a synthetic anthracycline anticancer drug widely used in the treatment of some hematological malignancies. The studies in our laboratory have clearly demonstrated that idarubicin can undergo reductive bioactivation by NADPH-cytochrome P450 reductase to free radicals with resulting formation of DNA strand breaks, which can potentially contribute to its genotoxic effects [Çelik, H., Arinç, E., Bioreduction of idarubicin and formation of ROS responsible for DNA cleavage by NADPH-cytochrome P450 reductase and its potential role in the antitumor effect. J Pharm Pharm Sci, 11(4):68-82, 2008]. In the current study, our aim was to investigate the possible protective effects of several phenolic antioxidants, quercetin, rutin, naringenin, resveratrol and trolox, against the DNA-damaging effect of idarubicin originating from its P450 reductase-catalyzed bioactivation. METHODS. DNA damage was measured by detecting single-strand breaks in plasmid pBR322 DNA using a cell-free agarose gel method. RESULTS. Our results indicated that, among the compounds tested, quercetin was the most potent antioxidant in preventing DNA damage. Quercetin significantly decreased the extent of DNA strand breaks in a dose-dependent manner; 100 μM of quercetin almost completely inhibited the DNA strand breakage. Unlike quercetin, its glycosidated conjugate rutin, failed to provide any significant protection against idarubicin-induced DNA strand breaks except at the highest concentration tested (2 mM). The protective effects of other antioxidants were significantly less than that of quercetin even at high concentrations. Quercetin was found to be also an effective protector against DNA damage induced by mitomycin C. CONCLUSION. We conclude that quercetin, one of the most abundant flavonoids in the human diet, is highly effective in reducing the DNA damage caused by the antitumor agents, idarubicin and mitomycin C, following bioactivation by P450 reductase.

Chemical regulation of abscisic acid catabolism in plants by cytochrome P450 inhibitors

2005 ◽  
Vol 13 (14) ◽  
pp. 4491-4498 ◽  
Author(s):  
Nobutaka Kitahata ◽  
Shigeki Saito ◽  
Yutaka Miyazawa ◽  
Taishi Umezawa ◽  
Yukihisa Shimada ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Abscisic Acid ◽  
Chemical Regulation ◽  
P450 Inhibitors

Whole-cell amperometric biosensor for screening of cytochrome P450 inhibitors

2016 ◽  
Vol 223 ◽  
pp. 392-399 ◽  
Author(s):  
Tal Yoetz-Kopelman ◽  
Carmit Porat-Ophir ◽  
Yosi Shacham-Diamand ◽  
Amihay Freeman
Keyword(s):  
Cytochrome P450 ◽  
Amperometric Biosensor ◽  
Whole Cell ◽  
P450 Inhibitors

scholarly journals Effects of cytochrome P450 inhibitors on EDHF-mediated relaxation in the rat hepatic artery

1996 ◽  
Vol 118 (5) ◽  
pp. 1147-1152 ◽  
Author(s):  
Peter M. Zygmunt ◽  
Gillian Edwards ◽  
Arthur H. Weston ◽  
S. Christopher Davis ◽  
Edward D. Högestätt
Keyword(s):  
Cytochrome P450 ◽  
Hepatic Artery ◽  
P450 Inhibitors

scholarly journals Effects of cytochrome P450 inhibitors on potassium currents and mechanical activity in rat portal vein

1996 ◽  
Vol 119 (4) ◽  
pp. 691-701 ◽  
Author(s):  
Gillian Edwards ◽  
Peter M. Zygmunt ◽  
Edward D. Högestätt ◽  
Arthur H. Weston
Keyword(s):  
Cytochrome P450 ◽  
Portal Vein ◽  
Potassium Currents ◽  
Mechanical Activity ◽  
Rat Portal Vein ◽  
P450 Inhibitors
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