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Mini-Reviews in Medicinal Chemistry

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ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

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Review Article

A Review on Vitamin E Natural Analogues and on the Design of Synthetic Vitamin E Derivatives as Cytoprotective Agents

Author(s): Panagiotis Theodosis-Nobelos, Georgios Papagiouvannis and Eleni A. Rekka*

Volume 21, Issue 1, 2021

Published on: 07 August, 2020

Page: [10 - 22] Pages: 13

DOI: 10.2174/1389557520666200807132617

Price: $65

Abstract

Vitamin E, essential for human health, is widely used worldwide for therapeutic or dietary reasons. The differences in the metabolism and excretion of the multiple vitamin E forms are presented in this review. The important steps that influence the kinetics of each form and the distribution and processing of vitamin E forms by the liver are considered. The antioxidant as well as non-antioxidant properties of vitamin E forms are discussed. Finally, synthetic tocopherol and trolox derivatives, based on the design of multitarget directed compounds, are reviewed. It is demonstrated that selected derivatization of vitamin E or trolox structures can produce improved antioxidants, agents against cancer, cardiovascular and neurodegenerative disorders.

Keywords: Vitamin E, tocopherols, tocotrienols, metabolism, transport, antioxidants, trolox, synthetic analogues.

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[1]
Evans, H.M.; Bishop, K.S. On the existence of a hitherto unrecognized dietary factor essential for reproduction. Science, 1922, 56(1458), 650-651.
[http://dx.doi.org/10.1126/science.56.1458.650] [PMID: 17838496]
[2]
Packer, L. Vitamin E is nature’s master antioxidant. Sci. Am. Sci. Med., 1994, 1, 54-63.
[3]
Mustacich, D.J.; Leonard, S.W.; Devereaux, M.W.; Sokol, R.J.; Traber, M.G. α-tocopherol regulation of hepatic cytochrome P450s and ABC transporters in rats. Free Radic. Biol. Med., 2006, 41(7), 1069-1078.
[http://dx.doi.org/10.1016/j.freeradbiomed.2006.06.022 ] [PMID: 16962932]
[4]
Miller, E.R., III; Pastor-Barriuso, R.; Dalal, D.; Riemersma, R.A.; Appel, L.J.; Guallar, E. Meta-analysis: High-dosage vitamin E supplementation may increase all-cause mortality. Ann. Intern. Med., 2005, 142(1), 37-46.
[http://dx.doi.org/10.7326/0003-4819-142-1-200501040-00110] [PMID: 15537682]
[5]
Cardenas, E.; Ghosh, R. Vitamin E: a dark horse at the crossroad of cancer management. Biochem. Pharmacol., 2013, 86(7), 845-852.
[http://dx.doi.org/10.1016/j.bcp.2013.07.018] [PMID: 23919929]
[6]
Sen, C.K.; Khanna, S.; Roy, S. Tocotrienols in health and disease: the other half of the natural vitamin E family. Mol. Aspects Med., 2007, 28(5-6), 692-728.
[http://dx.doi.org/10.1016/j.mam.2007.03.001] [PMID: 17507086]
[7]
Shils, M.E.; Shike, M.; Ross, A.C.; Caballero, B.; Cousins, R.J. Modern Nutrition in Health and Disease, 11th ed; Lippincott Williams and Wilkins: Philadelphia, USA, 2012.
[8]
Schmölz, L.; Birringer, M.; Lorkowski, S.; Wallert, M. Complexity of vitamin E metabolism. World J. Biol. Chem., 2016, 7(1), 14-43.
[http://dx.doi.org/10.4331/wjbc.v7.i1.14] [PMID: 26981194]
[9]
Rigotti, A. Absorption, transport, and tissue delivery of vitamin E. Mol. Aspects Med., 2007, 28(5-6), 423-436.
[http://dx.doi.org/10.1016/j.mam.2007.01.002] [PMID: 17320165]
[10]
Traber, M.G. Mechanisms for the prevention of vitamin E excess. J. Lipid Res., 2013, 54(9), 2295-2306.
[http://dx.doi.org/10.1194/jlr.R032946] [PMID: 23505319]
[11]
Bruno, R.S.; Leonard, S.W.; Park, S-I.; Zhao, Y.; Traber, M.G. Human vitamin E requirements assessed with the use of apples fortified with deuterium-labeled α-tocopheryl acetate. Am. J. Clin. Nutr., 2006, 83(2), 299-304.
[http://dx.doi.org/10.1093/ajcn/83.2.299] [PMID: 16469987]
[12]
Winklhofer-Roob, B.M.; Tuchschmid, P.E.; Molinari, L.; Shmerling, D.H. Response to a single oral dose of all-rac-alpha-tocopheryl acetate in patients with cystic fibrosis and in healthy individuals. Am. J. Clin. Nutr., 1996, 63(5), 717-721.
[http://dx.doi.org/10.1093/ajcn/63.5.717] [PMID: 8615354]
[13]
Muller, D.P.; Lloyd, J.K.; Wolff, O.H. Vitamin E and neurological function. Lancet, 1983, 1(8318), 225-228.
[http://dx.doi.org/10.1016/S0140-6736(83)92598-9] [PMID: 6130255]
[14]
Rader, D.J.; Brewer, H.B., Jr A beta lipoproteinemia: New insights into lipoprotein assembly and vitamin E metabolism from a rare genetic disease. JAMA, 1993, 270(7), 865-869.
[http://dx.doi.org/10.1001/jama.1993.03510070087042 ] [PMID: 8340987]
[15]
Narushima, K.; Takada, T.; Yamanashi, Y.; Suzuki, H. Niemann-pick C1-like 1 mediates alpha-tocopherol transport. Mol. Pharmacol., 2008, 74(1), 42-49.
[http://dx.doi.org/10.1124/mol.107.043034] [PMID: 18403720]
[16]
Hacquebard, M.; Carpentier, Y.A.; Vitamin, E. Absorption, plasma transport and cell uptake. Curr. Opin. Clin. Nutr. Metab. Care, 2005, 8(2), 133-138.
[http://dx.doi.org/10.1097/00075197-200503000-00005 PMID: 15716790]
[17]
Jiang, X.C.; Jin, W.; Hussain, M.M. The impact of Phospholipid Transfer Protein (PLTP) on lipoprotein metabolism. Nutr. Metab. (Lond.), 2012, 9(1), 75.
[http://dx.doi.org/10.1186/1743-7075-9-75] [PMID: 22897926]
[18]
Jiang, X.C.; Tall, A.R.; Qin, S.; Lin, M.; Schneider, M.; Lalanne, F.; Deckert, V.; Desrumaux, C.; Athias, A.; Witztum, J.L.; Lagrost, L. Phospholipid transfer protein deficiency protects circulating lipoproteins from oxidation due to the enhanced accumulation of vitamin E. J. Biol. Chem., 2002, 277(35), 31850-31856.
[http://dx.doi.org/10.1074/jbc.M205077200] [PMID: 12105225]
[19]
Traber, M.G.; Sokol, R.J.; Burton, G.W.; Ingold, K.U.; Papas, A.M.; Huffaker, J.E.; Kayden, H.J. Impaired ability of patients with familial isolated vitamin E deficiency to incorporate alpha-tocopherol into lipoproteins secreted by the liver. J. Clin. Invest., 1990, 85(2), 397-407.
[http://dx.doi.org/10.1172/JCI114452] [PMID: 2298915]
[20]
IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). Nomenclature of tocopherols and related compounds. Recommendations 1981. Mol. Cell. Biochem., 1982, 49(3), 183-185.
[PMID: 7162509]
[21]
Hosomi, A.; Arita, M.; Sato, Y.; Kiyose, C.; Ueda, T.; Igarashi, O.; Arai, H.; Inoue, K. Affinity for alpha-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs. FEBS Lett., 1997, 409(1), 105-108.
[http://dx.doi.org/10.1016/S0014-5793(97)00499-7] [PMID: 9199513]
[22]
Panagabko, C.; Morley, S.; Hernandez, M.; Cassolato, P.; Gordon, H.; Parsons, R.; Manor, D.; Atkinson, J. Ligand specificity in the CRAL-TRIO protein family. Biochemistry, 2003, 42(21), 6467-6474.
[http://dx.doi.org/10.1021/bi034086v] [PMID: 12767229]
[23]
Traber, M.G.; Atkinson, J. Vitamin E, antioxidant and nothing more. Free Radic. Biol. Med., 2007, 43(1), 4-15.
[http://dx.doi.org/10.1016/j.freeradbiomed.2007.03.024 ] [PMID: 17561088]
[24]
Traber, M.G.; Sokol, R.J.; Kohlschütter, A.; Yokota, T.; Muller, D.P.; Dufour, R.; Kayden, H.J. Impaired discrimination between stereoisomers of α-tocopherol in patients with familial isolated vitamin E deficiency. J. Lipid Res., 1993, 34(2), 201-210.
[PMID: 8429255]
[25]
Sato, Y.; Arai, H.; Miyata, A.; Tokita, S.; Yamamoto, K.; Tanabe, T.; Inoue, K. Primary structure of alpha-tocopherol transfer protein from rat liver. Homology with cellular retinaldehyde-binding protein. J. Biol. Chem., 1993, 268(24), 17705-17710.
[PMID: 8349655]
[26]
Qian, J.; Morley, S.; Wilson, K.; Nava, P.; Atkinson, J.; Manor, D. Intracellular trafficking of vitamin E in hepatocytes: The role of tocopherol transfer protein. J. Lipid Res., 2005, 46(10), 2072-2082.
[http://dx.doi.org/10.1194/jlr.M500143-JLR200] [PMID: 16024914]
[27]
Bjørneboe, A.; Bjørneboe, G.E.; Bodd, E.; Hagen, B.F.; Kveseth, N.; Drevon, C.A. Transport and distribution of alpha-tocopherol in lymph, serum and liver cells in rats. Biochim. Biophys. Acta, 1986, 889(3), 310-315.
[http://dx.doi.org/10.1016/0167-4889(86)90193-X] [PMID: 3790578]
[28]
Thurnham, D.I.; Davies, J.A.; Crump, B.J.; Situnayake, R.D.; Davis, M. The use of different lipids to express serum tocopherol: Lipid ratios for the measurement of vitamin E status. Ann. Clin. Biochem., 1986, 23(Pt 5), 514-520.
[http://dx.doi.org/10.1177/000456328602300505] [PMID: 3767286]
[29]
Kayden, H.J. Tocopherol content of adipose tissue from vitamin E deficient humans, in Porter, R. Whelan, J. (Eds.), Biology of Vitamin E; Pittman Books London, 1983, 70-91.
[30]
Sokol, R.J.; Heubi, J.E.; Iannaccone, S.T.; Bove, K.E.; Balistreri, W.F. Vitamin E deficiency with normal serum vitamin E concentrations in children with chronic cholestasis. N. Engl. J. Med., 1984, 310(19), 1209-1212.
[http://dx.doi.org/10.1056/NEJM198405103101901 ] [PMID: 6709026]
[31]
Rosenson, R.S.; Brewer, H.B., Jr; Davidson, W.S.; Fayad, Z.A.; Fuster, V.; Goldstein, J.; Hellerstein, M.; Jiang, X.C.; Phillips, M.C.; Rader, D.J.; Remaley, A.T.; Rothblat, G.H.; Tall, A.R.; Yvan-Charvet, L. Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport. Circulation, 2012, 125(15), 1905-1919.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.111.066589] [PMID: 22508840]
[32]
Bjornson, L.K.; Gniewkowski, C.; Kayden, H.J. Comparison of exchange of alpha-tocopherol and free cholesterol between rat plasma lipoproteins and erythrocytes. J. Lipid Res., 1975, 16(1), 39-53.
[PMID: 162930]
[33]
Parks, E.J.; Dare, D.; Frazier, K.B.; Hellerstein, M.K.; Neese, R.A.; Hughes, E.; Traber, M.G. Dependence of plasma α-tocopherol flux on very low-density triglyceride clearance in humans. Free Radic. Biol. Med., 2000, 29(11), 1151-1159.
[http://dx.doi.org/10.1016/S0891-5849(00)00426-3 ] [PMID: 11121723]
[34]
Eisengart, A.; Milhorat, A.T.; Simon, E.J.; Sundheim, L. The metabolism of vitamin E. II. Purification and characterization of urinary metabolites of alpha-tocopherol. J. Biol. Chem., 1956, 221(2), 807-817.
[PMID: 13357475]
[35]
Gross, C.S.; Milhorat, A.T.; Simon, E.J. The metabolism of vitamin E. I. The absorption and excretion of d-α-tocopheryl-5-methyl-C14-succinate. J. Biol. Chem., 1956, 221(2), 797-805.
[PMID: 13357474]
[36]
Eisengart, A.; Milhorat, A.T.; Simon, E.J.; Sundheim, L. The metabolism of vitamin E. II. Purification and characterization of urinary metabolites of α-tocopherol. J. Biol. Chem., 1956, 221(2), 807-817.
[PMID: 13357475]
[37]
Sharma, G.; Muller, D.; O’Riordan, S.; Bryan, S.; Hindmarsh, P.; Dattani, M.; Mills, K. A novel method for the direct measurement of urinary conjugated metabolites of alpha-tocopherol and its use in diabetes. Mol. Nutr. Food Res., 2010, 54(5), 599-600.
[http://dx.doi.org/10.1002/mnfr.200900378] [PMID: 20169581]
[38]
Mustacich, D.J.; Leonard, S.W.; Patel, N.K.; Traber, M.G. α-tocopherol β-oxidation localized to rat liver mitochondria. Free Radic. Biol. Med., 2010, 48(1), 73-81.
[http://dx.doi.org/10.1016/j.freeradbiomed.2009.10.024 ] [PMID: 19819327]
[39]
Birringer, M.; Pfluger, P.; Kluth, D.; Landes, N.; Brigelius-Flohé, R. Identities and differences in the metabolism of tocotrienols and tocopherols in HepG2 cells. J. Nutr., 2002, 132(10), 3113-3118.
[http://dx.doi.org/10.1093/jn/131.10.3113] [PMID: 12368403]
[40]
Diepeveen, S.H.; Verhoeven, G.W.; Van Der Palen, J.; Dikkeschei, L.D.; Van Tits, L.J.; Kolsters, G.; Offerman, J.J.; Bilo, H.J.; Stalenhoef, A.F. Effects of atorvastatin and vitamin E on lipoproteins and oxidative stress in dialysis patients: A randomised-controlled trial. J. Intern. Med., 2005, 257(5), 438-445.
[http://dx.doi.org/10.1111/j.1365-2796.2005.01484.x ] [PMID: 15836660]
[41]
Werba, J.P.; Cavalca, V.; Veglia, F.; Massironi, P.; De Franceschi, M.; Zingaro, L.; Tremoli, E. A new compound-specific pleiotropic effect of statins: Modification of plasma gamma-tocopherol levels. Atherosclerosis, 2007, 193(1), 229-233.
[http://dx.doi.org/10.1016/j.atherosclerosis.2006.06.020 ] [PMID: 16860808]
[42]
McDonald, M.G.; Rieder, M.J.; Nakano, M.; Hsia, C.K.; Rettie, A.E. CYP4F2 is a vitamin K1 oxidase: An explanation for altered warfarin dose in carriers of the V433M variant. Mol. Pharmacol., 2009, 75(6), 1337-1346.
[http://dx.doi.org/10.1124/mol.109.054833] [PMID: 19297519]
[43]
Shearer, M.J.; Newman, P. Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis. J. Lipid Res., 2014, 55(3), 345-362.
[http://dx.doi.org/10.1194/jlr.R045559] [PMID: 24489112]
[44]
Card, D.J.; Gorska, R.; Cutler, J.; Harrington, D.J. Vitamin K metabolism: Current knowledge and future research. Mol. Nutr. Food Res., 2014, 58(8), 1590-1600.
[http://dx.doi.org/10.1002/mnfr.201300683] [PMID: 24376012]
[45]
Jiang, Q.; Christen, S.; Shigenaga, M.K.; Ames, B.N. gamma-tocopherol, the major form of vitamin E in the US diet, deserves more attention. Am. J. Clin. Nutr., 2001, 74(6), 714-722.
[http://dx.doi.org/10.1093/ajcn/74.6.714] [PMID: 11722951]
[46]
Jiang, Q. Natural forms of vitamin E: Metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy. Free Radic. Biol. Med., 2014, 72, 76-90.
[http://dx.doi.org/10.1016/j.freeradbiomed.2014.03.035 ] [PMID: 24704972]
[47]
Yue, Y.; Novianti, M.L.; Tessensohn, M.E.; Hirao, H.; Webster, R.D.; Webster, R.D. Optimizing the lifetimes of phenoxonium cations derived from vitamin E via structural modifications. Org. Biomol. Chem., 2015, 13(48), 11732-11739.
[http://dx.doi.org/10.1039/C5OB01868D] [PMID: 26480893]
[48]
Kamal-Eldin, A.; Appelqvist, L.A. The chemistry and antioxidant properties of tocopherols and tocotrienols. Lipids, 1996, 31(7), 671-701.
[http://dx.doi.org/10.1007/BF02522884] [PMID: 8827691]
[49]
Förstermann, U.; Sessa, W.C. Nitric oxide synthases: regulation and function. Eur. Heart J., 2012, 33(7), 829-837-837a-837d.
[http://dx.doi.org/10.1093/eurheartj/ehr304] [PMID: 21890489]
[50]
Marcourakis, T.; Camarini, R.; Kawamoto, E.M.; Scorsi, L.R.; Scavone, C. Peripheral biomarkers of oxidative stress in aging and Alzheimer’s disease. Dement. Neuropsychol., 2008, 2(1), 2-8.
[http://dx.doi.org/10.1590/S1980-57642009DN20100002 ] [PMID: 29213532]
[51]
Bartosz, G. Reactive oxygen species: Destroyers or messengers? Biochem. Pharmacol., 2009, 77(8), 1303-1315.
[http://dx.doi.org/10.1016/j.bcp.2008.11.009] [PMID: 19071092]
[52]
Cooney, R.V.; Harwood, P.J.; Franke, A.A.; Narala, K.; Sundström, A.K.; Berggren, P.O.; Mordan, L.J. Products of γ-tocopherol reaction with NO2 and their formation in rat insulinoma (RINm5F) cells. Free Radic. Biol. Med., 1995, 19(3), 259-269.
[http://dx.doi.org/10.1016/0891-5849(95)00019-T] [PMID: 7557540]
[53]
Christen, S.; Woodall, A.A.; Shigenaga, M.K.; Southwell-Keely, P.T.; Duncan, M.W.; Ames, B.N. gamma-tocopherol traps mutagenic electrophiles such as NO(X) and complements alpha-tocopherol: Physiological implications. Proc. Natl. Acad. Sci. USA, 1997, 94(7), 3217-3222.
[http://dx.doi.org/10.1073/pnas.94.7.3217] [PMID: 9096373]
[54]
Cooney, R.V.; Franke, A.A.; Harwood, P.J.; Hatch-Pigott, V.; Custer, L.J.; Mordan, L.J. γ-tocopherol detoxification of nitrogen dioxide: Superiority to α-tocopherol. Proc. Natl. Acad. Sci. USA, 1993, 90(5), 1771-1775.
[http://dx.doi.org/10.1073/pnas.90.5.1771] [PMID: 8446589]
[55]
Christen, S.; Gee, P.; Ames, B.N. Mutagenicity of nitric oxide in base pair-specific Salmonella tester strains: TA7000 series. Methods Enzymol., 1996, 269, 267-278.
[http://dx.doi.org/10.1016/S0076-6879(96)69027-2] [PMID: 8791655]
[56]
van der Vliet, A.; Eiserich, J.P.; O’Neill, C.A.; Halliwell, B.; Cross, C.E. Tyrosine modification by reactive nitrogen species: A closer look. Arch. Biochem. Biophys., 1995, 319(2), 341-349.
[http://dx.doi.org/10.1006/abbi.1995.1303] [PMID: 7786014]
[57]
Ferroni, F.; Maccaglia, A.; Pietraforte, D.; Turco, L.; Minetti, M. Phenolic antioxidants and the protection of low density lipoprotein from peroxynitrite-mediated oxidations at physiologic CO2. J. Agric. Food Chem., 2004, 52(10), 2866-2874.
[http://dx.doi.org/10.1021/jf034270n] [PMID: 15137827]
[58]
Packer, L.; Weber, S.U.; Rimbach, G. Molecular aspects of alpha-tocotrienol antioxidant action and cell signalling. J. Nutr., 2001, 131(2), 369S-373S.
[http://dx.doi.org/10.1093/jn/131.2.369S] [PMID: 11160563]
[59]
Wong, R.S.; Radhakrishnan, A.K. Tocotrienol research: Past into present. Nutr. Rev., 2012, 70(9), 483-490.
[http://dx.doi.org/10.1111/j.1753-4887.2012.00512.x ] [PMID: 22946849]
[60]
Azzi, A.; Stocker, A.; Vitamin, E. Non-antioxidant roles. Prog. Lipid Res., 2000, 39(3), 231-255.
[http://dx.doi.org/10.1016/S0163-7827(00)00006-0 PMID: 10799717]
[61]
Terashima, K.; Takaya, Y.; Niwa, M. Powerful antioxidative agents based on garcinoic acid from Garcinia kola. Bioorg. Med. Chem., 2002, 10(5), 1619-1625.
[http://dx.doi.org/10.1016/S0968-0896(01)00428-X ] [PMID: 11886823]
[62]
Wallert, M.; Schmölz, L.; Galli, F.; Birringer, M.; Lorkowski, S. Regulatory metabolites of vitamin E and their putative relevance for atherogenesis. Redox Biol., 2014, 2, 495-503.
[http://dx.doi.org/10.1016/j.redox.2014.02.002] [PMID: 24624339]
[63]
Lei, Y.; Wang, K.; Deng, L.; Chen, Y.; Nice, E.C.; Huang, C. Redox regulation of inflammation: old elements, a new story. Med. Res. Rev., 2015, 35(2), 306-340.
[http://dx.doi.org/10.1002/med.21330] [PMID: 25171147]
[64]
Vanderhoek, J.Y.; Lands, W.E. The inhibition of the fatty acid oxygenase of sheep vesicular gland by antioxidants. Biochim. Biophys. Acta, 1973, 296(2), 382-385.
[http://dx.doi.org/10.1016/0005-2760(73)90096-9] [PMID: 4734625]
[65]
Beharka, A.A.; Wu, D.; Serafini, M.; Meydani, S.N. Mechanism of vitamin E inhibition of cyclooxygenase activity in macrophages from old mice: Role of peroxynitrite. Free Radic. Biol. Med., 2002, 32(6), 503-511.
[http://dx.doi.org/10.1016/S0891-5849(01)00817-6 ] [PMID: 11958951]
[66]
Rietjens, I.M.; Boersma, M.G.; Haan, Ld.; Spenkelink, B.; Awad, H.M.; Cnubben, N.H.; van Zanden, J.J.; Woude, Hv.; Alink, G.M.; Koeman, J.H. The pro-oxidant chemistry of the natural antioxidants vitamin C, vitamin E, carotenoids and flavonoids. Environ. Toxicol. Pharmacol., 2002, 11(3-4), 321-333.
[http://dx.doi.org/10.1016/S1382-6689(02)00003-0 ] [PMID: 21782615]
[67]
Halliwell, B.; Gutteridge, J. Free radicals in biology and medicine, 3rd ed; Clarendon Press: Oxford, 1999.
[68]
Liu, Z.Q. The “unexpected role” of vitamin E in free radical-induced hemolysis of human erythrocytes: alpha-tocopherol-mediated peroxidation. Cell Biochem. Biophys., 2006, 44(2), 233-239.
[http://dx.doi.org/10.1385/CBB:44:2:233] [PMID: 16456225]
[69]
Azzi, A. Many tocopherols, one vitamin E. Mol. Aspects Med., 2018, 61, 92-103.
[http://dx.doi.org/10.1016/j.mam.2017.06.004] [PMID: 28624327]
[70]
Kurumbail, R.G.; Kiefer, J.R.; Marnett, L.J. Cyclooxygenase enzymes: Catalysis and inhibition. Curr. Opin. Struct. Biol., 2001, 11(6), 752-760.
[http://dx.doi.org/10.1016/S0959-440X(01)00277-9 PMID: 11751058]
[71]
Jiang, Q.; Yin, X.; Lill, M.A.; Danielson, M.L.; Freiser, H.; Huang, J. Long-chain carboxychromanols, metabolites of vitamin E, are potent inhibitors of cyclooxygenases. Proc. Natl. Acad. Sci. USA, 2008, 105(51), 20464-20469.
[http://dx.doi.org/10.1073/pnas.0810962106] [PMID: 19074288]
[72]
Jiang, Z.; Yin, X.; Jiang, Q. Natural forms of vitamin E and 13′-carboxychromanol, a long-chain vitamin E metabolite, inhibit leukotriene generation from stimulated neutrophils by blocking calcium influx and suppressing 5-lipoxygenase activity, respectively. J. Immunol., 2011, 186(2), 1173-1179.
[http://dx.doi.org/10.4049/jimmunol.1002342] [PMID: 21169551]
[73]
Grau, A.; Ortiz, A. Dissimilar protection of tocopherol isomers against membrane hydrolysis by phospholipase A2. Chem. Phys. Lipids, 1998, 91(2), 109-118.
[http://dx.doi.org/10.1016/S0009-3084(97)00101-1] [PMID: 9569615]
[74]
Wagner, J.G.; Jiang, Q.; Harkema, J.R.; Ames, B.N.; Illek, B.; Roubey, R.A.; Peden, D.B. Gamma-tocopherol prevents airway eosinophilia and mucous cell hyperplasia in experimentally induced allergic rhinitis and asthma. Clin. Exp. Allergy, 2008, 38(3), 501-511.
[http://dx.doi.org/10.1111/j.1365-2222.2007.02855.x ] [PMID: 17970781]
[75]
Pantzaris, M.C.; Loukaides, G.N.; Ntzani, E.E.; Patrikios, I.S. A novel oral nutraceutical formula of omega-3 and omega-6 fatty acids with vitamins (PLP10) in relapsing remitting multiple sclerosis: A randomised, double-blind, placebo-controlled proof-of-concept clinical trial. BMJ Open, 2013, 3(4)e002170
[http://dx.doi.org/10.1136/bmjopen-2012-002170] [PMID: 23599375]
[76]
Kim, H.S.; Arai, H.; Arita, M.; Sato, Y.; Ogihara, T.; Inoue, K.; Mino, M.; Tamai, H. Effect of alpha-tocopherol status on alpha-tocopherol transfer protein expression and its messenger RNA level in rat liver. Free Radic. Res., 1998, 28(1), 87-92.
[http://dx.doi.org/10.3109/10715769809097879] [PMID: 9554836]
[77]
Munteanu, A.; Zingg, J.M.; Azzi, A. Anti-atherosclerotic effects of vitamin E--myth or reality? J. Cell. Mol. Med., 2004, 8(1), 59-76.
[http://dx.doi.org/10.1111/j.1582-4934.2004.tb00260.x ] [PMID: 15090261]
[78]
Raspor, P.; Plesničar, S.; Gazdag, Z.; Pesti, M.; Miklavcic, M.; Lah, B.; Logar-Marinsek, R.; Poljsak, B. Prevention of intracellular oxidation in yeast: The role of vitamin E analogue, Trolox (6-hydroxy-2,5,7,8-tetramethylkroman-2-carboxyl acid). Cell Biol. Int., 2005, 29(1), 57-63.
[http://dx.doi.org/10.1016/j.cellbi.2004.11.010] [PMID: 15763500]
[79]
Theodosis-Nobelos, P.; Kourounakis, P.N.; Rekka, E.A. Anti-inflammatory and hypolipidemic effect of novel conjugates with trolox and other antioxidant acids. Med. Chem., 2017, 13(3), 214-225.
[http://dx.doi.org/10.2174/1573406412666161104122310 ] [PMID: 27823562]
[80]
Mabile, L.; Fitoussi, G.; Periquet, B.; Schmitt, A.; Salvayre, R.; Nègre-Salvayre, A. alpha-Tocopherol and trolox block the early intracellular events (TBARS and calcium rises) elicited by oxidized low density lipoproteins in cultured endothelial cells. Free Radic. Biol. Med., 1995, 19(2), 177-187.
[http://dx.doi.org/10.1016/0891-5849(95)00006-J] [PMID: 7649489]
[81]
Burkitt, M.J.; Milne, L. Hydroxyl radical formation from Cu(II)-trolox mixtures: Insights into the pro-oxidant properties of α-tocopherol. FEBS Lett., 1996, 379(1), 51-54.
[http://dx.doi.org/10.1016/0014-5793(95)01481-0] [PMID: 8566228]
[82]
Prasad, K.N.; Kumar, B.; Yan, X.D.; Hanson, A.J.; Cole, W.C. Alpha-tocopheryl succinate, the most effective form of vitamin E for adjuvant cancer treatment: A review. J. Am. Coll. Nutr., 2003, 22(2), 108-117.
[http://dx.doi.org/10.1080/07315724.2003.10719283 ] [PMID: 12672706]
[83]
Zakharova, O.D.; Frolova, T.S.; Yushkova, Y.V.; Chernyak, E.I.; Pokrovsky, A.G.; Pokrovsky, M.A.; Morozov, S.V.; Sinitsina, O.I.; Grigor’ev, I.A.; Nevinsky, G.A. Antioxidant and antitumor activity of trolox, trolox succinate, and α-tocopheryl succinate conjugates with nitroxides. Eur. J. Med. Chem., 2016, 122, 127-137.
[http://dx.doi.org/10.1016/j.ejmech.2016.05.051] [PMID: 27344490]
[84]
Singh, V.P.; Poon, J.F.; Engman, L. Catalytic antioxidants: Regenerable tellurium analogues of vitamin E. Org. Lett., 2013, 15(24), 6274-6277.
[http://dx.doi.org/10.1021/ol403131t] [PMID: 24279415]
[85]
Battioni, J.P.; Fontecave, M.; Jaouen, M.; Mansuy, D. Vitamin E derivatives as new potent inhibitors of microsomal lipid peroxidation. Biochem. Biophys. Res. Commun., 1991, 174(3), 1103-1108.
[http://dx.doi.org/10.1016/0006-291X(91)91534-J] [PMID: 1996979]
[86]
Lars, J.; Nilsson, G.; Selander, H.; Sievertsson, H.; Skånberg, I. The directing effect of annelated rings in aromatic systems. II. Synthesis and oxidation of 2,3-dihydro-5-benzofuranols. I. An apparent Mills-Nixon effect in oxidative coupling of phenols. Tetrahedron, 1970, 26(3), 879-886.
[http://dx.doi.org/10.1016/S0040-4020(01)97886-X ] [PMID: 5435927]
[87]
Cohen, N.; Schaer, B.; Saucy, G.; Borer, R.; Todaro, L.; Marie Chiu, A.M. Lewis acid mediated nucleophilic substitution reactions of 2-alkoxy-3,4-dihydro-2H-1-benzopyrans: Regiochemistry and utility in the synthesis of 3,4-dihydro-2H-1-benzopyran-2-carboxylic acids. J. Org. Chem., 1989, 54, 3282-3292.
[http://dx.doi.org/10.1021/jo00275a010]
[88]
Ingold, K.U.; Burton, G.W.; Foster, D.O.; Zuker, M.; Hughes, L.; Lacelle, S.; Lusztyk, E.; Slaby, M. A new vitamin E analogue more active than alpha-tocopherol in the rat curative myopathy bioassay. FEBS Lett., 1986, 205(1), 117-120.
[http://dx.doi.org/10.1016/0014-5793(86)80877-8] [PMID: 3743765]
[89]
Manfredini, S.; Vertuani, S.; Manfredi, B.; Rossoni, G.; Calviello, G.; Palozza, P. Novel antioxidant agents deriving from molecular combinations of vitamins C and E analogues: 3,4-dihydroxy-5(R)-[2(R,S)-(6-hydroxy-2,5,7,8-tetramethyl-chroman-2(R,S)-yl-methyl)-[1,3]dioxolan-4(S)-yl]-5H-furan-2-one and 3-O-octadecyl derivatives. Bioorg. Med. Chem., 2000, 8, 2791-2801.
[http://dx.doi.org/10.1016/S0968-0896(00)00205-4 ] [PMID: 11131170]
[90]
Arai, T.; Ohno, A.; Kazunori, M.; Kakizawa, T.; Kuwata, H.; Ozawa, T.; Shibanuma, M.; Hara, S.; Ishida, S.; Kurihara, M.; Miyata, N.; Nakagawa, H.; Fukuhara, K. Design, synthesis, and evaluation of Trolox-conjugated amyloid-β C-terminal peptides for therapeutic intervention in an in vitro model of Alzheimer’s disease. Bioorg. Med. Chem., 2016, 24(18), 4138-4143.
[http://dx.doi.org/10.1016/j.bmc.2016.06.057] [PMID: 27407032]
[91]
Xie, S.S.; Lan, J.S.; Wang, X.B.; Jiang, N.; Dong, G.; Li, Z.R.; Wang, K.D.; Guo, P.P.; Kong, L.Y. Multifunctional tacrine-trolox hybrids for the treatment of Alzheimer’s disease with cholinergic, antioxidant, neuroprotective and hepatoprotective properties. Eur. J. Med. Chem., 2015, 93, 42-50.
[http://dx.doi.org/10.1016/j.ejmech.2015.01.058] [PMID: 25656088]
[92]
Nepovimova, E.; Korabecny, J.; Dolezal, R.; Babkova, K.; Ondrejicek, A.; Jun, D.; Sepsova, V.; Horova, A.; Hrabinova, M.; Soukup, O.; Bukum, N.; Jost, P.; Muckova, L.; Kassa, J.; Malinak, D.; Andrs, M.; Kuca, K. Tacrine-trolox hybrids: A novel class of centrally active, nonhepatotoxic multi-target-directed ligands exerting anticholinesterase and antioxidant activities with low in vivo toxicity. J. Med. Chem., 2015, 58(22), 8985-9003.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01325] [PMID: 26503905]
[93]
Koufaki, M.; Calogeropoulou, T.; Rekka, E.; Chryselis, M.; Papazafiri, P.; Gaitanaki, C.; Makriyannis, A. Bifunctional agents for reperfusion arrhythmias: Novel hybrid vitamin E/class I antiarrhythmics. Bioorg. Med. Chem., 2003, 11(23), 5209-5219.
[http://dx.doi.org/10.1016/j.bmc.2003.08.010] [PMID: 14604685]
[94]
Koufaki, M.; Detsi, A.; Theodorou, E.; Kiziridi, C.; Calogeropoulou, T.; Vassilopoulos, A.; Kourounakis, A.P.; Rekka, E.; Kourounakis, P.N.; Gaitanaki, C.; Papazafiri, P. Synthesis of chroman analogues of lipoic acid and evaluation of their activity against reperfusion arrhythmias. Bioorg. Med. Chem., 2004, 12(18), 4835-4841.
[http://dx.doi.org/10.1016/j.bmc.2004.07.012] [PMID: 15336262]
[95]
Theodosis-Nobelos, P.; Athanasekou, C.; Rekka, E.A. Dual antioxidant structures with potent anti-inflammatory, hypolipidemic and cytoprotective properties. Bioorg. Med. Chem. Lett., 2017, 27(21), 4800-4804.
[http://dx.doi.org/10.1016/j.bmcl.2017.09.054] [PMID: 29017787]
[96]
Shimizu, K.; Kondo, R.; Sakai, K.; Takeda, N.; Nagahata, T.; Oniki, T. Novel vitamin E derivative with 4-substituted resorcinol moiety has both antioxidant and tyrosinase inhibitory properties. Lipids, 2001, 36(12), 1321-1326.
[http://dx.doi.org/10.1007/s11745-001-0847-9] [PMID: 11834083]
[97]
Tsiakitzis, K.; Kourounakis, A.P.; Tani, E.; Rekka, E.A.; Kourounakis, P.N. Stress and active oxygen species--effect of alpha-tocopherol on stress response. Arch. Pharm. (Weinheim), 2005, 338(7), 315-321.
[http://dx.doi.org/10.1002/ardp.200400946] [PMID: 15981300]
[98]
Tsiakitzis, K.C.; Rekka, E.A.; Kourounakis, A.P.; Kourounakis, P.N. Novel compounds designed as antistress agents. J. Med. Chem., 2009, 52(22), 7315-7318.
[http://dx.doi.org/10.1021/jm901169b] [PMID: 19863055]
[99]
Theodosis-Nobelos, P.; Papagiouvannis, G.; Kourounakis, P.N.; Rekka, E.A. Active anti-inflammatory and hypolipidemic derivatives of lorazepam. Molecules, 2019, 24(18)E3277
[http://dx.doi.org/10.3390/molecules24183277] [PMID: 31505754]
[100]
Tsiakitzis, K.C.; Papagiouvannis, G.; Theodosis-Nobelos, P.; Tziona, P.; Kourounakis, P.N.; Rekka, E.A. Synthesis, antioxidant and anti-inflammatoy effects of antioxidant acid amides with GABA and N-acyl-pyrrolidin-2-ones. Curr. Chem. Biol., 2017, 11, 127-139.
[http://dx.doi.org/10.2174/2212796811666170509123209]

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