Phytochemistry Reviews

, 10:353 | Cite as

The chemical and biological activities of quinones: overview and implications in analytical detection

  • Nahed El-Najjar
  • Hala Gali-Muhtasib
  • Raimo A. Ketola
  • Pia Vuorela
  • Arto Urtti
  • Heikki Vuorela


Quinones are a class of natural and synthetic compounds that have several beneficial effects. Quinones are electron carriers playing a role in photosynthesis. As vitamins, they represent a class of molecules preventing and treating several illnesses such as osteoporosis and cardiovascular diseases. Quinones, by their antioxidant activity, improve general health conditions. Many of the drugs clinically approved or still in clinical trials against cancer are quinone related compounds. Quinones have also toxicological effects through their presence as photoproducts from air pollutants. Quinones are fast redox cycling molecules and have the potential to bind to thiol, amine and hydroxyl groups. The aforementioned properties make the analytical detection of quinones problematic. However, recent advances of the available analytical techniques along with the possibility of using labeled compound facilitate their detection hence allowing a better understanding of their action. This review summarizes the current knowledge with respect to the oxido-reductive and electrophilic properties of quinones as well as to the analytical tools used for their analysis. It includes a general introduction about the physiological, and therapeutical functions of quinones. A number of studies are reported to cover the chemical reactivity in an attempt to understand quinones as biologically active compounds. Data ranging from normal analytical methods to study quinones derived from plant or biological matrices to the use of labeled compounds are presented. The examples illustrate how chemical, biological and analytical knowledge can be integrated to have a better understanding of the mode of action of the quinones.


Quinone Chemotherapeutic agents One electron reduction Two electron reduction Labeled compounds analysis 



Miss Soha Rimane is highly acknowledged for her help in revising the English of the review.


  1. Ahmed S, Kishikawa N, Nakashima K et al (2007) Determination of vitamin K homologues by high-performance liquid chromatography with on-line photoreactor and peroxyoxalate chemiluminescence detection. Anal Chim Acta 591:148–154PubMedCrossRefGoogle Scholar
  2. Ahmed S, Kishikawa N, Ohyama K et al (2009) An ultrasensitive and highly selective determination method for quinones by high-performance liquid chromatography with photochemically initiated luminol chemiluminescence. J Chromatogr A 1216:3977–3984PubMedCrossRefGoogle Scholar
  3. Alvarez-Cedron L, Sayalero ML, Lanao JM (1999) High-performance liquid chromatographic validated assay of doxorubicin in rat plasma and tissues. J Chromatogr B Biomed Sci Appl 721:271–278PubMedCrossRefGoogle Scholar
  4. Asche C (2005) Antitumour quinones. Mini Rev Med Chem 5:449–467PubMedCrossRefGoogle Scholar
  5. Atasayar S, Gurer-Orhan H, Orhan H et al (2008) Preventive effect of aminoguanidine compared to vitamin E and C on cisplatin-induced nephrotoxicity in rats. Exp Toxicol Pathol 61:23–32PubMedCrossRefGoogle Scholar
  6. Azharuddin MK, O’Reilly DS, Gray A et al (2007) HPLC method for plasma vitamin K1: effect of plasma triglyceride and acute-phase response on circulating concentrations. Clin Chem 53:1706–1713PubMedCrossRefGoogle Scholar
  7. Bailey SM, Lewis AD, Patterson LH et al (2001) Involvement of NADPH: cytochrome P450 reductase in the activation of indoloquinone EO9 to free radical and DNA damaging species. Biochem Pharmacol 62:461–468PubMedCrossRefGoogle Scholar
  8. Bakasso S, Lamien-Meda A, Lamien CE et al (2008) Polyphenol contents and antioxidant activities of five Indigofera species (Fabaceae) from Burkina Faso. Pak J Biol Sci 11:1429–1435PubMedCrossRefGoogle Scholar
  9. Bartoszek A, Wolf CR (1992) Enhancement of doxorubicin toxicity following activation by NADPH cytochrome P450 reductase. Biochem Pharmacol 43:1449–1457PubMedCrossRefGoogle Scholar
  10. Beattie JR, Maguire C, Gilchrist S et al (2007) The use of Raman microscopy to determine and localize vitamin E in biological samples. FASEB J 21:766–776PubMedCrossRefGoogle Scholar
  11. Begleiter A, Leith MK, Patel D et al (2007) Role of NADPH cytochrome P450 reductase in activation of RH1. Cancer Chemother Pharmacol 60:713–723PubMedCrossRefGoogle Scholar
  12. Belcourt MF, Hodnick WF, Rockwell S et al (1998) Exploring the mechanistic aspects of mitomycin antibiotic bioactivation in Chinese hamster ovary cells overexpressing NADPH:cytochrome C (P-450) reductase and DT-diaphorase. Adv Enzyme Regul 38:111–133PubMedCrossRefGoogle Scholar
  13. Benzakour O (2008) Vitamin K-dependent proteins: functions in blood coagulation and beyond. Thromb Haemost 100:527–529PubMedGoogle Scholar
  14. Beulens JW, Bots ML, Atsma F et al (2008) High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis 203:489–493PubMedCrossRefGoogle Scholar
  15. Bianchet MA, Faig M, Amzel LM (2004) Structure and mechanism of NAD[P]H:quinone acceptor oxidoreductases (NQO). Methods Enzymol 382:144–174PubMedCrossRefGoogle Scholar
  16. Bianchet MA, Erdemli SB, Amzel LM (2008) Structure, function, and mechanism of cytosolic quinone reductases. Vitam Horm 78:63–84PubMedCrossRefGoogle Scholar
  17. Bjornsson TD, Meffin PJ, Swezey SE et al (1979) Effects of clofibrate and warfarin alone and in combination on the disposition of vitamin K1. J Pharmacol Exp Ther 210:322–326PubMedGoogle Scholar
  18. Bolhaar ST, Mulder M, van Ginkel CJ (2001) IgE-mediated allergy to henna. Allergy 56:248PubMedCrossRefGoogle Scholar
  19. Bolognia JL, Sodi SA, Osber MP et al (1995) Enhancement of the depigmenting effect of hydroquinone by cystamine and buthionine sulfoximine. Br J Dermatol 133:349–357PubMedCrossRefGoogle Scholar
  20. Breton J, Nabedryk E (1996) Protein-quinone interactions in the bacterial photosynthetic reaction center: light-induced FTIR difference spectroscopy of the quinone vibrations. 1275:84–90Google Scholar
  21. Bringmann G, Mutanyatta-Comar J, Knauer M et al (2008) Knipholone and related 4-phenylanthraquinones: structurally, pharmacologically, and biosynthetically remarkable natural products. Nat Prod Rep 25:696–718PubMedCrossRefGoogle Scholar
  22. Buffinton GD, Ollinger K, Brunmark A et al (1989) DT-diaphorase-catalysed reduction of 1, 4-naphthoquinone derivatives and glutathionyl-quinone conjugates. Effect of substituents on autoxidation rates. Biochem J 257:561–571PubMedGoogle Scholar
  23. Bugel S (2008) Vitamin K and bone health in adult humans. Vitam Horm 78:393–416PubMedCrossRefGoogle Scholar
  24. Cadenas E (1995) Antioxidant and prooxidant functions of DT-diaphorase in quinone metabolism. Biochem Pharmacol 49:127–140PubMedCrossRefGoogle Scholar
  25. Cai Y, Lu J, Miao Z et al (2007) Reactive oxygen species contribute to cell killing and P-glycoprotein downregulation by salvicine in multidrug resistant K562/A02 cells. Cancer Biol Ther 6:1794–1799PubMedCrossRefGoogle Scholar
  26. Cai YJ, Lu JJ, Zhu H et al (2008) Salvicine triggers DNA double-strand breaks and apoptosis by GSH-depletion-driven H2O2 generation and topoisomerase II inhibition. Free Radic Biol Med 45:627–635PubMedCrossRefGoogle Scholar
  27. Calogiuri G, Foti C, Bonamonte D et al (2010) Allergic reactions to henna-based temporary tattoos and their components. Immunopharmacol Immunotoxicol 32:700–704PubMedCrossRefGoogle Scholar
  28. Carrasco IJ, Marquez MC, Xue Y et al (2008) Sediminibacillus halophilus gen. nov., sp. nov., a moderately halophilic, Gram-positive bacterium from a hypersaline lake. Int J Syst Evol Microbiol 58:1961–1967PubMedCrossRefGoogle Scholar
  29. Celik H, Arinç E (2008) 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 11:68–82PubMedGoogle Scholar
  30. Chan TS, O’Brien PJ (2003) Hepatocyte metabolism of coenzyme Q1 (ubiquinone-5) to its sulfate conjugate decreases its antioxidant activity. Biofactors 18:207–218PubMedCrossRefGoogle Scholar
  31. Chen X, Gardner ER, Gutierrez M et al (2007) Determination of 17-dimethylaminoethylamino-17-demethoxygeldanamycin in human plasma by liquid chromatography with mass-spectrometric detection. J Chromatogr B Analyt Technol Biomed Life Sci 858:302–306PubMedCrossRefGoogle Scholar
  32. Chinje EC, Patterson AV, Saunders MP et al (1999) Does reductive metabolism predict response to tirapazamine (SR 4233) in human non-small-cell lung cancer cell lines? Br J Cancer 81:1127–1133PubMedCrossRefGoogle Scholar
  33. Chung SH, Chung SM, Lee JY et al (1999) The biological significance of non-enzymatic reaction of menadione with plasma thiols: enhancement of menadione-induced cytotoxicity to platelets by the presence of blood plasma. FEBS Lett 449:235–240PubMedCrossRefGoogle Scholar
  34. Clarke MW, Burnett JR, Croft KD (2008) Vitamin E in human health and disease. Crit Rev Clin Lab Sci 45:417–450PubMedCrossRefGoogle Scholar
  35. Cleren C, Yang L, Lorenzo B et al (2008) Therapeutic effects of coenzyme Q10 (CoQ10) and reduced CoQ10 in the MPTP model of Parkinsonism. J Neurochem 104:1613–1621PubMedCrossRefGoogle Scholar
  36. Cordoba-Pedregosa Mdel C, Villalba JM, Alcain FJ (2005) Determination of coenzyme Q biosynthesis in cultured cells without the necessity for lipid extraction. Anal Biochem 336:60–63PubMedCrossRefGoogle Scholar
  37. Cowen RL, Patterson AV, Telfer BA et al (2003) Viral delivery of P450 reductase recapitulates the ability of constitutive overexpression of reductase enzymes to potentiate the activity of mitomycin C in human breast cancer xenografts. Mol Cancer Ther 2:901–909PubMedGoogle Scholar
  38. Cullinane C, Cutts SM, van Rosmalen A et al (1994) Formation of adriamycin-DNA adducts in vitro. Nucleic Acids Res 22:2296–2303PubMedCrossRefGoogle Scholar
  39. Cummings J, Ritchie A, Butler J et al (2003) Activity profile of the novel aziridinylbenzoquinones MeDZQ and RH1 in human tumour xenografts. Anticancer Res 23:3979–3983PubMedGoogle Scholar
  40. Cysyk RL, Parker RJ, Barchi JJ Jr et al (2006) Reaction of geldanamycin and C17-substituted analogues with glutathione: product identifications and pharmacological implications. Chem Res Toxicol 19:376–381PubMedCrossRefGoogle Scholar
  41. Danson S, Johnson P, Ward T et al. (2011) Phase I pharmacokinetic and pharmacodynamic study of the bioreductive drug RH1. Ann Oncol Epub (ahead of print)Google Scholar
  42. Daozhen C, Lu L, Min Y et al (2007) Synthesis of (131)I-labeled-[(131)I]iodo-17-allylamino-17-demethoxy geldanamycin ([(131)I]iodo-17-AAG) and its biodistribution in mice. Cancer Biother Radiopharm 22:607–612PubMedCrossRefGoogle Scholar
  43. Davidson RT, Foley AL, Engelke JA et al (1998) Conversion of dietary phylloquinone to tissue menaquinone-4 in rats is not dependent on gut bacteria. J Nutr 128:220–223PubMedGoogle Scholar
  44. Dey PM, Harborne JB (1989) Methods in plant biochemistry. In: Harborne JB (ed) Plant phenolics. Academic Press, London, pp 452–791Google Scholar
  45. Dolnikowski GG, Sun Z, Grusak MA et al (2002) HPLC and GC/MS determination of deuterated vitamin K (phylloquinone) in human serum after ingestion of deuterium-labeled broccoli. J Nutr Biochem 13:168–174PubMedCrossRefGoogle Scholar
  46. El Sohly MA, Gul W, Murphy TP (2004) Analysis of the anthraquinones aloe-emodin and aloin by gas chromatography/mass spectrometry. Int Immunopharmacol 4:1739–1744CrossRefGoogle Scholar
  47. Erkkila AT, Lichtenstein AH, Dolnikowski GG et al (2004) Plasma transport of vitamin K in men using deuterium-labeled collard greens. Metabolism 53:215–221PubMedCrossRefGoogle Scholar
  48. Fahmy OT, Korany MA, Maher HM (2004) High performance liquid chromatographic determination of some co-administered anticancer drugs in pharmaceutical preparations and in spiked human plasma. J Pharm Biomed Anal 34:1099–1107PubMedCrossRefGoogle Scholar
  49. Gaikwad NW, Rogan EG, Cavalieri EL (2007) Evidence from ESI-MS for NQO1-catalyzed reduction of estrogen ortho-quinones. Free Radic Biol Med 43:1289–1298PubMedCrossRefGoogle Scholar
  50. Gali-Muhtasib H, Kuester D, Mawrin C et al (2008a) Thymoquinone triggers inactivation of the stress response pathway sensor CHEK1 and contributes to apoptosis in colorectal cancer cells. Cancer Res 68:5609–5618PubMedCrossRefGoogle Scholar
  51. Gali-Muhtasib H, Ocker M, Kuester D et al (2008b) Thymoquinone reduces mouse colon tumor cell invasion and inhibits tumor growth in murine colon cancer models. J Cell Mol Med 12:330–342PubMedCrossRefGoogle Scholar
  52. Gong X, Gutala R, Jaiswal AK (2008) Quinone oxidoreductases and vitamin K metabolism. Vitam Horm 78:85–101PubMedCrossRefGoogle Scholar
  53. Guo W, Reigan P, Siegel D et al (2008) Enzymatic reduction and glutathione conjugation of benzoquinone ansamycin heat shock protein 90 inhibitors: relevance for toxicity and mechanism of action. Drug Metab Dispos 36:2050–2057PubMedCrossRefGoogle Scholar
  54. Halamova K, Kokoska L, Flesar J et al (2010) In vitro antifungal effect of black cumin seed quinones against dairy spoilage yeasts at different acidity levels. J Food Prot 73:2291–2295PubMedGoogle Scholar
  55. Hao H, Wang G, Cui N et al (2007) Identification of a novel intestinal first pass metabolic pathway: NQO1 mediated quinone reduction and subsequent glucuronidation. Curr Drug Metab 8:137–149PubMedCrossRefGoogle Scholar
  56. Hasinoff BB, Begleiter A (2006) The reductive activation of the antitumor drug RH1 to its semiquinone free radical by NADPH cytochrome P450 reductase and by HCT116 human colon cancer cells. Free Radic Res 40:974–978PubMedCrossRefGoogle Scholar
  57. Holtz KM, Rockwell S, Tomasz M et al (2003) Nuclear overexpression of NADH:cytochrome b5 reductase activity increases the cytotoxicity of mitomycin C(MC) and the total number of MC-DNA adducts in Chinese hamster ovary cells. J Biol Chem 278:5029–5034PubMedCrossRefGoogle Scholar
  58. Hsieh YJ, Lin LC, Tsai TH (2006) Measurement and pharmacokinetic study of plumbagin in a conscious freely moving rat using liquid chromatography/tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 844:1–5PubMedCrossRefGoogle Scholar
  59. Ito S, Wakamatsu K (2008) Chemistry of mixed melanogenesis—pivotal roles of dopaquinone. Photochem Photobiol 84:582–592PubMedCrossRefGoogle Scholar
  60. Jaiswal AK (1994) Human NAD(P)H:quinone oxidoreductase2. Gene structure, activity, and tissue-specific expression. J Biol Chem 269:14502–14508PubMedGoogle Scholar
  61. Jaiswal AK, Burnett P, Adesnik M et al (1990) Nucleotide and deduced amino acid sequence of a human cDNA (NQO2) corresponding to a second member of the NAD(P)H: quinone oxidoreductase gene family. Extensive polymorphism at the NQO2 gene locus on chromosome 6. Biochemistry 29:1899–1906PubMedCrossRefGoogle Scholar
  62. Jakoby WB, Ziegler DM (1990) The enzymes of detoxication. J Biol Chem 265:20715–20718PubMedGoogle Scholar
  63. Johnston JS, Phelps MA, Blum KA et al (2008) Development and validation of a rapid and sensitive high-performance liquid chromatography-mass spectroscopy assay for determination of 17-(allylamino)-17-demethoxygeldanamycin and 17-(amino)-17-demethoxygeldanamycin in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci 871:15–21PubMedCrossRefGoogle Scholar
  64. Jones KS, Bluck LJ, Coward WA (2006) Analysis of isotope ratios in vitamin K1 (phylloquinone) from human plasma by gas chromatography/mass spectrometry. Rapid Commun Mass Spectrom 20:1894–1898PubMedCrossRefGoogle Scholar
  65. Joseph P, Jaiswal AK (1994) NAD(P)H:quinone oxidoreductase1 (DT diaphorase) specifically prevents the formation of benzo[a]pyrene quinone-DNA adducts generated by cytochrome P4501A1 and P450 reductase. Proc Natl Acad Sci USA 91:8413–8417PubMedCrossRefGoogle Scholar
  66. Joseph P, Xu Y, Jaiswal AK (1996) Non-enzymatic and enzymatic activation of mitomycin C: identification of a unique cytosolic activity. Int J Cancer 65:263–271PubMedCrossRefGoogle Scholar
  67. Kamao M, Suhara Y, Tsugawa N et al (2007) Vitamin K content of foods and dietary vitamin K intake in Japanese young women. J Nutr Sci Vitaminol (Tokyo) 53:464–470CrossRefGoogle Scholar
  68. Kang W, Jeong JH, Ma E et al (2007) Simple and sensitive determination of menatetrenone and its epoxide metabolite in human plasma. J Pharm Biomed Anal 44:1178–1182PubMedCrossRefGoogle Scholar
  69. Kappus H (1986) Overview of enzyme systems involved in bio-reduction of drugs and in redox cycling. Biochem Pharmacol 35:1–6PubMedCrossRefGoogle Scholar
  70. Kappus H, Sies H (1981) Toxic drug effects associated with oxygen metabolism: redox cycling and lipid peroxidation. Experientia 37:1233–1241PubMedCrossRefGoogle Scholar
  71. Karpinska J, Mikoluc B, Motkowski R et al (2006) HPLC method for simultaneous determination of retinol, alpha-tocopherol and coenzyme Q10 in human plasma. J Pharm Biomed Anal 42:232–236PubMedCrossRefGoogle Scholar
  72. Kasraee B, Handjani F, Aslani FS (2003) Enhancement of the depigmenting effect of hydroquinone and 4-hydroxyanisole by all-trans-retinoic acid (tretinoin): the impairment of glutathione-dependent cytoprotection? Dermatology 206:289–291PubMedCrossRefGoogle Scholar
  73. Kim MK, Park MJ, Im WT et al (2008) Aeromicrobium ginsengisoli sp. nov., isolated from a ginseng field. Int J Syst Evol Microbiol 58:2025–2030PubMedCrossRefGoogle Scholar
  74. Koka PS, Mondal D, Schultz M et al (2010) Studies on molecular mechanisms of growth inhibitory effects of thymoquinone against prostate cancer cells: role of reactive oxygen species. Exp Biol Med 235:751–760CrossRefGoogle Scholar
  75. Kostrzewa-Nowak D, Paine MJ, Wolf CR et al (2005) The role of bioreductive activation of doxorubicin in cytotoxic activity against leukaemia HL60-sensitive cell line and its multidrug-resistant sublines. Br J Cancer 93:89–97PubMedCrossRefGoogle Scholar
  76. Kurilich AC, Britz SJ, Clevidence BA et al (2003) Isotopic labeling and LC-APCI-MS quantification for investigating absorption of carotenoids and phylloquinone from kale (Brassica oleracea). J Agric Food Chem 51:4877–4883PubMedCrossRefGoogle Scholar
  77. Land EJ, Ramsden CA, Riley PA (2004) Quinone chemistry and melanogenesis. Methods Enzymol 378:88–109PubMedCrossRefGoogle Scholar
  78. Lanham-New SA (2008) Importance of calcium, vitamin D and vitamin K for osteoporosis prevention and treatment. Proc Nutr Soc 67:163–176PubMedCrossRefGoogle Scholar
  79. Lenta BN, Weniger B, Antheaume C et al (2007) Anthraquinones from the stem bark of Stereospermum zenkeri with antimicrobial activity. Phytochemistry 68:1595–1599PubMedCrossRefGoogle Scholar
  80. Lepoittevin JP, Benezra C (1991) Allergic contact dermatitis caused by naturally occurring quinones. Pharm Weekbl Sci 13:119–122PubMedGoogle Scholar
  81. Li WW, Heinze J, Haehnel W (2005) Site-specific binding of quinones to proteins through thiol addition and addition-elimination reactions. J Am Chem Soc 127:6140–6141PubMedCrossRefGoogle Scholar
  82. Li Y, Zhang H, Fawcett JP et al (2007) Quantitation and metabolism of mitoquinone, a mitochondria-targeted antioxidant, in rat by liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 21:1958–1964PubMedCrossRefGoogle Scholar
  83. Lim JH, Kim KM, Kim SW et al (2008) Bromocriptine activates NQO1 via Nrf2-PI3 K/Akt signaling: novel cytoprotective mechanism against oxidative damage. Pharmacol Res 57:325–331PubMedCrossRefGoogle Scholar
  84. Lind C (1985) Formation of benzo[a]pyrene-3, 6-quinol mono- and diglucuronides in rat liver microsomes. Arch Biochem Biophys 240:226–235PubMedCrossRefGoogle Scholar
  85. Lu Y, Zhang J, Qian J (2008) The effect of emodin on VEGF receptors in human colon cancer cells. Cancer Biother Radiopharm 23:222–228PubMedCrossRefGoogle Scholar
  86. Lubitz W (2003) Photochemical processes in photosynthesis studied by advanced electron paramagnetic resonance techniques. Pure Appl Chem 75:1021–1030CrossRefGoogle Scholar
  87. Magee PS (2000) Exploring the chemistry of quinones by computation. Quant Struct Act Relat 19:22–28CrossRefGoogle Scholar
  88. Malkinson AM, Siegel D, Forrest GL et al (1992) Elevated DT-diaphorase activity and messenger RNA content in human non-small cell lung carcinoma: relationship to the response of lung tumor xenografts to mitomycin Cl. Cancer Res 52:4752–4757PubMedGoogle Scholar
  89. Mallakin A, McConkey BJ, Miao G et al (1999) Impacts of structural photomodification on the toxicity of environmental contaminants: anthracene photooxidation products. Ecotoxicol Environ Saf 43:204–212PubMedCrossRefGoogle Scholar
  90. Mallakin A, Dixon DG, Greenberg BM (2000) Pathway of anthracene modification under simulated solar radiation. Chemosphere 40:1435–1441PubMedCrossRefGoogle Scholar
  91. Mansour M, Tornhamre S (2004) Inhibition of 5-lipoxygenase and leukotriene C4 synthase in human blood cells by thymoquinone. J Enzyme Inhib Med Chem 19:431–436PubMedCrossRefGoogle Scholar
  92. Marinho-Filho J, Bezerra D, Araújo A et al (2010) Oxidative stress induction by (+)-cordiaquinone J triggers both mitochondria-dependent apoptosis and necrosis in leukemia cells. Chem Biol Interact 183:369–379PubMedCrossRefGoogle Scholar
  93. Martinez VG, Williams KJ, Stratford IJ et al (2008) Overexpression of cytochrome P450 NADPH reductase sensitises MDA 231 breast carcinoma cells to 5-fluorouracil: possible mechanisms involved. Toxicol In Vitro 22:582–588PubMedCrossRefGoogle Scholar
  94. Mazuel C, Grove J, Gerin G et al (2003) HPLC-MS/MS determination of a peptide conjugate prodrug of doxorubicin, and its active metabolites, leucine-doxorubicin and doxorubicin, in dog and rat plasma. J Pharm Biomed Anal 33:1093–1102PubMedCrossRefGoogle Scholar
  95. McGaw LJ, Lall N, Hlokwe TM et al (2008) Purified compounds and extracts from Euclea species with antimycobacterial activity against Mycobacterium bovis and fast-growing mycobacteria. Biol Pharm Bull 31:1429–1433PubMedCrossRefGoogle Scholar
  96. Miao XS, Song P, Savage RE et al (2008) Identification of the in vitro metabolites of 3, 4-dihydro-2, 2-dimethyl-2H-naphthol[1, 2-b]pyran-5, 6-dione (ARQ 501; beta-lapachone) in whole blood. Drug Metab Dispos 36:641–648PubMedCrossRefGoogle Scholar
  97. Mikami K, Naito M, Ishiguro T et al (1998) Immunological quantitation of DT-diaphorase in carcinoma cell lines and clinical colon cancers: advanced tumors express greater levels of DT-diaphorase. Jpn J Cancer Res 89:910–915PubMedGoogle Scholar
  98. Monks TJ, Jones DC (2002) The metabolism and toxicity of quinones, quinonimines, quinone methides, and quinone-thioethers. Curr Drug Metab 3:425–438PubMedCrossRefGoogle Scholar
  99. Moreno-Farre J, Asad Y, Pacey S et al (2006) Development and validation of a liquid chromatography/tandem mass spectrometry method for the determination of the novel anticancer agent 17-DMAG in human plasma. Rapid Commun Mass Spectrom 20:2845–2850PubMedCrossRefGoogle Scholar
  100. Murty VS, Penning TM (1992) Polycyclic aromatic hydrocarbon (PAH) ortho-quinone conjugate chemistry: kinetics of thiol addition to PAH ortho-quinones and structures of thioether adducts of naphthalene-1, 2-dione. Chem Biol Interact 84:169–188PubMedCrossRefGoogle Scholar
  101. Nageswara Rao R, Kumar Talluri MV, Shinde DD (2008) Simultaneous separation and determination of coenzyme Q(10) and its process related impurities by NARP-HPLC and atmospheric pressure chemical ionization-mass spectrometry (APCI-MS). J Pharm Biomed Anal 47:230–237PubMedCrossRefGoogle Scholar
  102. Nemeikaite-Ceniene A, Sarlauskas J, Anusevicius Z et al (2003) Cytotoxicity of RH1 and related aziridinylbenzoquinones: involvement of activation by NAD(P)H:quinone oxidoreductase (NQO1) and oxidative stress. Arch Biochem Biophys 416:110–118PubMedCrossRefGoogle Scholar
  103. Nishiyama T, Ohnuma T, Inoue Y et al (2008) UDP-glucuronosyltransferases 1A6 and 1A10 catalyze reduced menadione glucuronidation. Biochem Biophys Res Commun 371:247–250PubMedCrossRefGoogle Scholar
  104. Ojha A, Rathod R, Padh H (2009) Simultaneous HPLC-UV determination of rhein and aceclofenac in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci 877:1145–1148PubMedCrossRefGoogle Scholar
  105. Okano T, Shimomura Y, Yamane M et al (2008) Conversion of phylloquinone (Vitamin K1) into menaquinone-4 (Vitamin K2) in mice: two possible routes for menaquinone-4 accumulation in cerebra of mice. J Biol Chem 283:11270–11279PubMedCrossRefGoogle Scholar
  106. Olson RE, Chao J, Graham D et al (2002) Total body phylloquinone and its turnover in human subjects at two levels of vitamin K intake. Br J Nutr 87:543–553PubMedCrossRefGoogle Scholar
  107. Pan SS, Andrews PA, Glover CJ et al (1984) Reductive activation of mitomycin C and mitomycin C metabolites catalyzed by NADPH-cytochrome P-450 reductase and xanthine oxidase. J Biol Chem 259:959–966PubMedGoogle Scholar
  108. Paramapojn S, Ganzera M, Gritsanapan W et al (2008) Analysis of naphthoquinone derivatives in the Asian medicinal plant Eleutherine americana by RP-HPLC and LC-MS. J Pharm Biomed Anal 47:990–993PubMedCrossRefGoogle Scholar
  109. Paroni R, Faioni EM, Razzari C et al (2009) Determination of vitamin K1 in plasma by solid phase extraction and HPLC with fluorescence detection. J Chromatogr B Analyt Technol Biomed Life Sci 877:351–354PubMedCrossRefGoogle Scholar
  110. Parrish DD, Schlosser MJ, Kapeghian JC et al (1997) Activation of CGS 12094 (prinomide metabolite) to 1, 4-benzoquinone by myeloperoxidase: implications for human idiosyncratic agranulocytosis. Fundam Appl Toxicol 35:197–204PubMedCrossRefGoogle Scholar
  111. Patterson AV, Barham HM, Chinje EC et al (1995) Importance of P450 reductase activity in determining sensitivity of breast tumour cells to the bioreductive drug, tirapazamine (SR 4233). Br J Cancer 72:1144–1150PubMedCrossRefGoogle Scholar
  112. Patterson AV, Saunders MP, Chinje EC et al (1997) Overexpression of human NADPH:cytochrome c (P450) reductase confers enhanced sensitivity to both tirapazamine (SR 4233) and RSU 1069. Br J Cancer 76:1338–1347PubMedCrossRefGoogle Scholar
  113. Pepe S, Marasco SF, Haas SJ et al (2007) Coenzyme Q10 in cardiovascular disease. Mitochondrion 7(Suppl):S154–S167PubMedCrossRefGoogle Scholar
  114. Petersen KU (2002) From toxic precursors to safe drugs. Mechanisms and relevance of idiosyncratic drug reactions. Arzneimittelforschung 52:423–429PubMedGoogle Scholar
  115. Qian G, Leung SY, Lu G et al (2008) Optimization and validation of a chromatographic method for the simultaneous quantification of six bioactive compounds in Rhizoma et Radix Polygoni Cuspidati. J Pharm Pharmacol 60:107–113PubMedCrossRefGoogle Scholar
  116. Radjendirane V, Joseph P, Lee YH et al (1998) Disruption of the DT diaphorase (NQO1) gene in mice leads to increased menadione toxicity. J Biol Chem 273:7382–7389PubMedCrossRefGoogle Scholar
  117. Rahman S, Bhatia K, Khan AQ et al (2008) Topically applied vitamin E prevents massive cutaneous inflammatory and oxidative stress responses induced by double application of 12-O-tetradecanoylphorbol-13-acetate (TPA) in mice. Chem Biol Interact 172:195–205PubMedCrossRefGoogle Scholar
  118. Raspotnig G, Leutgeb V, Schaider M et al (2010) Naphthoquinones and anthraquinones from scent glands of a dyspnoid Harvestman, Paranemastoma quadripunctatum. J Chem Ecol 36:158–162PubMedCrossRefGoogle Scholar
  119. Rizzo MR, Abbatecola AM, Barbieri M et al (2008) Evidence for anti-inflammatory effects of combined administration of vitamin E and C in older persons with impaired fasting glucose: impact on insulin action. J Am Coll Nutr 27:505–511PubMedGoogle Scholar
  120. Ronden JE, Drittij-Reijnders MJ, Vermeer C et al (1998) Intestinal flora is not an intermediate in the phylloquinone-menaquinone-4 conversion in the rat. Biochim Biophys Acta 1379:69–75PubMedGoogle Scholar
  121. Sakunphueak A, Panichayupakaranant P (2010) Simultaneous determination of three naphthoquinones in the leaves of Impatiens balsamina L. by reversed-phase high-performance liquid chromatography. Phytochem Anal 21:444–450PubMedCrossRefGoogle Scholar
  122. Salem ML (2005) Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int Immunopharmacol 5:1749–1770PubMedCrossRefGoogle Scholar
  123. Savage RE, Hall T, Bresciano K et al (2008) Development and validation of a liquid chromatography-tandem mass spectrometry method for the determination of ARQ 501 (beta-lapachone) in plasma and tumors from nu/nu mouse xenografts. J Chromatogr B Analyt Technol Biomed Life Sci 872:148–153PubMedCrossRefGoogle Scholar
  124. Savarino L, Fioravanti A, Leo G et al (2007) Anthraquinone-2, 6-disulfonic acid as a disease-modifying osteoarthritis drug: an in vitro and in vivo study. Clin Orthop Relat Res 461:231–237PubMedGoogle Scholar
  125. Sethi G, Ahn KS, Aggarwal BB (2008) Targeting nuclear factor-kappa B activation pathway by thymoquinone: role in suppression of antiapoptotic gene products and enhancement of apoptosis. Mol Cancer Res 6:1059–1070PubMedCrossRefGoogle Scholar
  126. Sharma N, Sharma UK, Malik S et al (2008) Isolation and purification of acetylshikonin and beta-acetoxyisovalerylshikonin from cell suspension cultures of Arnebia euchroma (Royle) Johnston using rapid preparative HPLC. J Sep Sci 31:629–635PubMedCrossRefGoogle Scholar
  127. Shearer MJ, Mallinson CN, Webster GR et al (1972) Clearance from plasma and excretion in urine, faeces and bile of an intravenous dose of tritiated vitamin K 1 in man. Br J Haematol 22:579–588PubMedCrossRefGoogle Scholar
  128. Shearer MJ, McBurney A, Barkhan P (1974) Studies on the absorption and metabolism of phylloquinone (vitamin K1) in man. Vitam Horm 32:513–542PubMedCrossRefGoogle Scholar
  129. Siegel D, Ross D (2000) Immunodetection of NAD(P)H:quinone oxidoreductase 1 (NQO1) in human tissues. Free Radic Biol Med 29:246–253PubMedCrossRefGoogle Scholar
  130. Siegel D, Franklin WA, Ross D (1998) Immunohistochemical detection of NAD(P)H:quinone oxidoreductase in human lung and lung tumors. Clin Cancer Res 4:2065–2070PubMedGoogle Scholar
  131. Singh H, Moore RE, Scheuer PJ (1967) The distribution of quinone pigments in echinoderms. Experientia 23:624–626PubMedCrossRefGoogle Scholar
  132. Skladanowski A, Konopa J (1994) Interstrand DNA crosslinking induced by anthracyclines in tumour cells. Biochem Pharmacol 47:2269–2278PubMedCrossRefGoogle Scholar
  133. Song Y, Buettner GR (2010) Thermodynamic and kinetic considerations for the reaction of semiquinone radicals to form superoxide and hydrogen peroxide. Free Radic Biol Med 49:919–962PubMedCrossRefGoogle Scholar
  134. Song K, Jeon S (2003) Modulation of hydrogen bonding through redox chemistry of quinones and urea-functionalized porphyrin. Bull Korean Chem Soc 24:153–154CrossRefGoogle Scholar
  135. Song R, Xu L, Xu F et al (2010) In vivo metabolism study of rhubarb decoction in rat using high-performance liquid chromatography with UV photodiode-array and mass-spectrometric detection: a strategy for systematic analysis of metabolites from traditional Chinese medicines in biological samples. J Chromatogr A 1217:7144–7152PubMedCrossRefGoogle Scholar
  136. Sottani C, Rinaldi P, Leoni E et al (2008) Simultaneous determination of cyclophosphamide, ifosfamide, doxorubicin, epirubicin and daunorubicin in human urine using high-performance liquid chromatography/electrospray ionization tandem mass spectrometry: bioanalytical method validation. Rapid Commun Mass Spectrom 22:2645–2659PubMedCrossRefGoogle Scholar
  137. Su CC, Chen GW, Kang JC et al (2008) Growth inhibition and apoptosis induction by tanshinone IIA in human colon adenocarcinoma cells. Planta Med 74:1357–1362PubMedCrossRefGoogle Scholar
  138. Takahashi Y, Kubota T, Ito J et al (2008) Nakijiquinones G-I, new sesquiterpenoid quinones from marine sponge. Bioorg Med Chem 16:7561–7564PubMedCrossRefGoogle Scholar
  139. Tampo Y, Yonaha M (1996) Enzymatic and molecular aspects of the antioxidant effect of menadione in hepatic microsomes. Arch Biochem Biophys 334:163–174PubMedCrossRefGoogle Scholar
  140. Thomson RH (1991) Distribution of naturally occurring quinones. Pharm Weekbl Sci 13:70–73PubMedGoogle Scholar
  141. Thor H, Smith MT, Hartzell P et al (1982) The metabolism of menadione (2-methyl-1, 4-naphthoquinone) by isolated hepatocytes. A study of the implications of oxidative stress in intact cells. J Biol Chem 257:12419–12425PubMedGoogle Scholar
  142. Vainchtein LD, Rosing H, Mirejovsky D et al (2008) Enhanced resolution triple-quadrupole mass spectrometry for ultra-sensitive and quantitative analysis of the investigational anticancer agent EO9 (apaziquone) and its metabolite EO5a in human and dog plasma to support (pre)-clinical studies of EOquin given intravesically. Rapid Commun Mass Spectrom 22:462–470PubMedCrossRefGoogle Scholar
  143. Van Ommen B, Koster A, Verhagen H et al (1992) The glutathione conjugates of tert-butyl hydroquinone as potent redox cycling agents and possible reactive agents underlying the toxicity of butylated hydroxyanisole. Biochem Biophys Res Commun 189:309–314PubMedCrossRefGoogle Scholar
  144. Venkatesh G, Ramanathan S, Mansor SM et al (2007) Development and validation of RP-HPLC-UV method for simultaneous determination of buparvaquone, atenolol, propranolol, quinidine and verapamil: a tool for the standardization of rat in situ intestinal permeability studies. J Pharm Biomed Anal 43:1546–1551PubMedCrossRefGoogle Scholar
  145. Venkatesh G, Majid MI, Ramanathan S et al (2008) Optimization and validation of RP-HPLC-UV method with solid-phase extraction for determination of buparvaquone in human and rabbit plasma: application to pharmacokinetic study. Biomed Chromatogr 22:535–541PubMedCrossRefGoogle Scholar
  146. Wallin R, Schurgers L, Wajih N (2008) Effects of the blood coagulation vitamin K as an inhibitor of arterial calcification. Thromb Res 122:411–417PubMedCrossRefGoogle Scholar
  147. Wang SL, Han JF, He XY et al (2007) Genetic variation of human cytochrome p450 reductase as a potential biomarker for mitomycin C-induced cytotoxicity. Drug Metab Dispos 35:176–179PubMedCrossRefGoogle Scholar
  148. Wang J, Li H, Jin C et al (2008) Development and validation of a UPLC method for quality control of rhubarb-based medicine: fast simultaneous determination of five anthraquinone derivatives. J Pharm Biomed Anal 47:765–770PubMedCrossRefGoogle Scholar
  149. Wang Y, Gray J, Mishin V et al (2010) Distinct roles of cytochrome P450 reductase in mitomycin C redox cycling and cytotoxicity. Mol Cancer Ther 9:1852–1863PubMedCrossRefGoogle Scholar
  150. Weber P (2001) Vitamin K and bone health. Nutrition 17:880–887PubMedCrossRefGoogle Scholar
  151. Wei W, Zhou Y, Wang X et al (2008a) Sphingobacterium anhuiense sp. nov., isolated from forest soil. Int J Syst Evol Microbiol 58:2098–2101PubMedCrossRefGoogle Scholar
  152. Wei X, Jiang JS, Feng ZM et al (2008b) Anthraquinone-benzisochromanquinone dimers from the roots of Berchemia floribunda. Chem Pharm Bull (Tokyo) 56:1248–1252CrossRefGoogle Scholar
  153. Wijeratne EM, Paranagama PA, Marron MT et al (2008) Sesquiterpene quinones and related metabolites from Phyllosticta spinarum, a fungal strain endophytic in Platycladus orientalis of the Sonoran Desert. J Nat Prod 71:218–222PubMedCrossRefGoogle Scholar
  154. Will BH, Usui Y, Suttie JW (1992) Comparative metabolism and requirement of vitamin K in chicks and rats. J Nutr 122:2354–2360PubMedGoogle Scholar
  155. Winski SL, Hargreaves RH, Butler J et al (1998) A new screening system for NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor quinones: identification of a new aziridinylbenzoquinone, RH1, as a NQO1-directed antitumor agent. Clin Cancer Res 4:3083–3088PubMedGoogle Scholar
  156. Workman P (1994) Enzyme-directed bioreductive drug development revisited: a commentary on recent progress and future prospects with emphasis on quinone anticancer agents and quinone metabolizing enzymes, particularly DT-diaphorase. Oncol Res 6:461–475PubMedGoogle Scholar
  157. Wu K, Knox R, Sun XZ et al (1997) Catalytic properties of NAD(P)H:quinone oxidoreductase-2 (NQO2), a dihydronicotinamide riboside dependent oxidoreductase. Arch Biochem Biophys 347:221–228PubMedCrossRefGoogle Scholar
  158. Xu F, Liu Y, Zhang Z et al (2008) Rapid simultaneous quantification of five active constituents in rat plasma by high-performance liquid chromatography/tandem mass spectrometry after oral administration of Da-Cheng-Qi decoction. J Pharm Biomed Anal 47:586–595PubMedCrossRefGoogle Scholar
  159. Xue X, You J, He P (2008) Simultaneous determination of five fat-soluble vitamins in feed by high-performance liquid chromatography following solid-phase extraction. J Chromatogr Sci 46:345–350PubMedGoogle Scholar
  160. Yan C, Kepa JK, Siegel D et al. (2008) Dissecting the role of multiple reductases in bioactivation and cytotoxicity of the antitumor agent RH1. Mol PharmacolGoogle Scholar
  161. Zhang Y, Chen X, Qin S et al (2006) LC-MS method for determination and pharmacokinetic study of chimaphilin in rat plasma after oral administration of the traditional Chinese medicinal preparation Lu xian cao decoction. Biol Pharm Bull 29:2523–2527PubMedCrossRefGoogle Scholar
  162. Zhang C, Ondeyka JG, Zink DL et al (2008) Isolation, structure, and antibacterial activity of phaeosphenone from a Phaeosphaeria sp. discovered by antisense strategy. J Nat Prod 71:1304–1307PubMedCrossRefGoogle Scholar
  163. Zhao Q, Yang XL, Holtzclaw WD et al (1997) Unexpected genetic and structural relationships of a long-forgotten flavoenzyme to NAD(P)H:quinone reductase (DT-diaphorase). Proc Natl Acad Sci USA 94:1669–1674PubMedCrossRefGoogle Scholar
  164. Zhao Y, Qin F, Boyd J et al (2010) Characterization and determination of chloro- and bromo-benzoquinones as new chlorination disinfection byproducts in drinking water. Anal Chem 82:4599–4605PubMedCrossRefGoogle Scholar
  165. Zhu Q, Emanuele MA, LaPaglia N et al (2007) Vitamin E prevents ethanol-induced inflammatory, hormonal, and cytotoxic changes in reproductive tissues. Endocrine 32:59–68PubMedCrossRefGoogle Scholar
  166. Zuo Y, Wang C, Lin Y et al (2008) Simultaneous determination of anthraquinones in radix Polygoni multiflori by capillary gas chromatography coupled with flame ionization and mass spectrometric detection. J Chromatogr A 1200:43–48PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Nahed El-Najjar
    • 1
  • Hala Gali-Muhtasib
    • 2
  • Raimo A. Ketola
    • 3
  • Pia Vuorela
    • 4
  • Arto Urtti
    • 3
  • Heikki Vuorela
    • 1
  1. 1.Division of Pharmaceutical Biology, Faculty of PharmacyUniversity of HelsinkiHelsinkiFinland
  2. 2.Department of BiologyAmerican University of BeirutBeirutLebanon
  3. 3.Center for Drug ResearchUniversity of HelsinkiHelsinkiFinland
  4. 4.Pharmaceutical Sciences, Department of BiosciencesAbo Akademi UniversityTurkuFinland

Personalised recommendations