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Current Organic Synthesis

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ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

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Research Article

Identification of Novel Sesamol Dimers with Unusual Methylenedioxy Ring-Opening Skeleton and Evaluation of Their Antioxidant and Cytotoxic Activities

Author(s): Sudtha Murthy, Ummi H.A.M. Hazli, Kin W. Kong, Chun-Wai Mai, Chee-Onn Leong, Noorsaadah A. Rahman, Kong M. Lo and Chin F. Chee*

Volume 16, Issue 8, 2019

Page: [1166 - 1173] Pages: 8

DOI: 10.2174/1570179416666191003095253

Price: $65

Abstract

Background: Sesamol is a widely used antioxidant for the food and pharmaceutical industries. The oxidation products of this compound may be accumulated in foods or ingested. Little is known about its effect on human health.

Objective: It is of great interest to identify the oxidation products of sesamol that may be beneficial to humans. This study was undertaken to identify the oxidation products of sesamol and investigate their antioxidant and cytotoxic activities.

Materials and Methods: Using the ferricyanide oxidation approach, four oxidation products of sesamol (2, 3, 20 & 21) have been identified. Structural elucidation of these compounds was established on the basis of their detailed NMR spectroscopic analysis, mass spectrometry and x-ray crystallography. Additionally, a formation mechanism of compound 20 was proposed based on high-resolution mass spectrometry-fragmentation method. The antioxidant activities of these compounds were determined by the DPPH, FRAP, and ABTS assays. The in vitro antiproliferative activity of these compounds was evaluated against a panel of human cancer cell lines as well as non-cancerous cells.

Results: Two oxidation products of sesamol were found to contain an unusual methylenedioxy ring-opening skeleton, as evidenced by spectroscopic and x-ray crystallographic data. Among all compounds, 20 displayed impressive antiproliferative activities against a panel of human cancer cell lines yet remained non-toxic to noncancerous cells. The antioxidant activities of compound 20 are significantly weaker than sesamol as determined by the DPPH, FRAP, and ABTS assays.

Conclusion: The oxidation products of sesamol could be a valuable source of bioactive molecules. Compound 20 may be used as a potential lead molecule for cancer studies.

Keywords: Bioactive compounds, structure elucidation, sesamol, oxidation, antioxidant, cytotoxic activity.

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[1]
Constantin, M.A.; Conrad, J.; Beifuss, U. An unprecedented oxidative trimerization of sesamol catalyzed by laccases. Tetrahedron Lett., 2012, 53(26), 3254-3258.
[http://dx.doi.org/10.1016/j.tetlet.2012.04.056]
[2]
Hewgill, F.R. Oxidation of alkoxyphenols—XXIV11Part XXIII: A dipheno-2,2′-quinone from sesamol. Tetrahedron, 1978, 34(10), 1595-1596.
[http://dx.doi.org/10.1016/0040-4020(78)80189-6]
[3]
Masuda, T.; Fujimoto, A.; Oyama, Y.; Maekawa, T.; Sone, Y. Structures of cytotoxic products from Fe-catalyzed oxidation of sesamol in ethanol. Tetrahedron Lett., 2009, 50(27), 3905-3908.
[http://dx.doi.org/10.1016/j.tetlet.2009.04.063]
[4]
Masuda, T.; Shingai, Y.; Fujimoto, A.; Nakamura, M.; Oyama, Y.; Maekawa, T.; Sone, Y. Identification of cytotoxic dimers in oxidation product from sesamol, a potent antioxidant of sesame oil. J. Agric. Food Chem., 2010, 58(20), 10880-10885.
[http://dx.doi.org/10.1021/jf103015j] [PMID: 20925385]
[5]
More, N.Y.; Jeganmohan, M. Solvent-controlled selective synthesis of biphenols and quinones via oxidative coupling of phenols. Chem. Commun. (Camb.), 2017, 53(69), 9616-9619.
[http://dx.doi.org/10.1039/C7CC04829G] [PMID: 28809969]
[6]
Lee, J.H.Q.; Tay, B.K.; Rakesh, G.; Richard, D.W. The Electrochemical oxidation of sesamol in acetonitrile containing variable amounts of Water. Electrochim. Acta, 2015, 184, 392-402.
[http://dx.doi.org/10.1016/j.electacta.2015.10.068]
[7]
Fujimoto, A.; Shingai, Y.; Oyama, T.B.; Kawanai, T.; Hashimoto, E.; Koizumi, K.; Kimura, K.; Masuda, T.; Oyama, Y. Apoptosis-inducing action of two products from oxidation of sesamol, an antioxidative constituent of sesame oil: A possible cytotoxicity of oxidized antioxidant. Toxicol. In Vitro, 2010, 24(6), 1720-1726.
[http://dx.doi.org/10.1016/j.tiv.2010.05.013] [PMID: 20510349]
[8]
Shingai, Y.; Fujimoto, A.; Nakajima, A.; Saito, A.; Kanemaru, K.; Masuda, T.; Oyama, Y. Cytotoxic characteristics of two isomeric dimers produced by oxidation of sesamol, an antioxidant in sesame oil. J. Health Sci., 2011, 57(5), 425-431.
[http://dx.doi.org/10.1248/jhs.57.425]
[9]
Kumar, C.M.; Sathisha, U.V.; Dharmesh, S.; Rao, A.G.A.; Singh, S.A. Interaction of sesamol (3,4-methylenedioxyphenol) with tyrosinase and its effect on melanin synthesis. Biochimie, 2011, 93(3), 562-569.
[http://dx.doi.org/10.1016/j.biochi.2010.11.014] [PMID: 21144881]
[10]
O’Brien, P.J. Molecular mechanisms of quinone cytotoxicity. Chem. Biol. Interact., 1991, 80(1), 1-41.
[http://dx.doi.org/10.1016/0009-2797(91)90029-7] [PMID: 1913977]
[11]
Choe, E.; Min, D.B. Mechanisms of Antioxidants in the Oxidation of Foods. Compr. Rev. Food Sci. Food Saf., 2009, 8(4), 345-358.
[http://dx.doi.org/10.1111/j.1541-4337.2009.00085.x]
[12]
Kurechi, T.; Kikugawa, K.; Aoshima, S. Studies on the Antioxidants. XIV.: reaction of sesamol with hydrogen peroxide-peroxidase. Chem. Pharm. Bull. (Tokyo), 1981, 29(8), 2351-2358.
[http://dx.doi.org/10.1248/cpb.29.2351]
[13]
Tamura, Y.; Yakura, T.; Haruta, J.; Kita, Y. Hypervalent iodine oxidation of para-alkoxyphenols and related-compounds - a general-route to para-benzoquinone monoacetals and spiro lactones. J. Org. Chem., 1987, 52(17), 3927-3930.
[http://dx.doi.org/10.1021/jo00226a041]
[14]
Sartori, G.; Maggi, R.; Bigi, F.; Arienti, A.; Casnati, G. Regiochemical control in the oxidative coupling of metal phenolates - highly selective synthesis of symmetrical, hydroxylated biaryls. Tetrahedron Lett., 1992, 33(16), 2207-2210.
[http://dx.doi.org/10.1016/0040-4039(92)88178-8]
[15]
Malkowsky, I.M.; Rommel, C.E.; Fröhlich, R.; Griesbach, U.; Pütter, H.; Waldvogel, S.R. Novel template-directed anodic phenol-coupling reaction. Chemistry, 2006, 12(28), 7482-7488.
[http://dx.doi.org/10.1002/chem.200600375] [PMID: 16874823]
[16]
Britoa, R.E.; Rodríguez, J.M.; Maldonado, P.; Ruiz Montoya, M.; Palma, A.; Morales, E. Elucidation of the electrochemical oxidation mechanism of the antioxidant sesamol on a glassy carbon electrode. J. Electrochem. Soc., 2014, 161(5), G27-G32.
[http://dx.doi.org/10.1149/2.028405jes]
[17]
Gandhi, M.; Rajagopal, D.; Parthasarathy, S.; Raja, S.; Huang, S.T.; Senthil Kumar, A. In Situ immobilized sesamol-quinone/carbon nanoblack-based electrochemical redox platform for efficient bioelectrocatalytic and immunosensor applications. ACS Omega, 2018, 3(9), 10823-10835.
[http://dx.doi.org/10.1021/acsomega.8b01296] [PMID: 30320253]
[18]
Brand-Williams, W.; Cuvelier, M.E.; Berset, C. Use of a free radical method to evaluate antioxidant activity. Lebensm. Wiss. Technol., 1995, 28, 25-30.
[http://dx.doi.org/10.1016/S0023-6438(95)80008-5]
[19]
Re, R.; Pellegrini, N.; Proteggente, A.; Pannala, A.; Yang, M.; Rice-Evans, C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic. Biol. Med., 1999, 26(9-10), 1231-1237.
[http://dx.doi.org/10.1016/S0891-5849(98)00315-3] [PMID: 10381194]
[20]
Benzie, I.F.F.; Strain, J.J. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal. Biochem., 1996, 239(1), 70-76.
[http://dx.doi.org/10.1006/abio.1996.0292] [PMID: 8660627]
[21]
Cole, E.R. Crank.G. and Minh.H.T.H. Oxidations with Lead-Tetraacetate. 3. Oxidations of 2-Substituted-1,3-Benzodioxoles. Aust. J. Chem., 1980, 33(7), 1553-1558.
[http://dx.doi.org/10.1071/CH9801553]
[22]
Lim, C.K.; Hemaroopini, S.; Gan, S.Y.; Loo, S.M.; Low, J.R.; Jong, Y.M.; Soo, H.C.; Leong, C.O.; Mai, C.W.; Chee, C.F. In vitro cytotoxic activity of isolated compounds from Malaysian Calophyllum species. Med. Chem. Res., 2016, 25(8), 1686-1694.
[http://dx.doi.org/10.1007/s00044-016-1606-y]
[23]
Al-Khdhairawi, A.A.Q.; Krishnan, P.; Mai, C.W.; Chung, F.F.; Leong, C.O.; Yong, K.T.; Chong, K.W.; Low, Y.Y.; Kam, T.S.; Lim, K.H. A Bis-benzopyrroloisoquinoline Alkaloid Incorporating a Cyclobutane Core and a Chlorophenanthroindolizidine Alkaloid with Cytotoxic Activity from Ficus fistulosa var. tengerensis. J. Nat. Prod., 2017, 80(10), 2734-2740.
[http://dx.doi.org/10.1021/acs.jnatprod.7b00500] [PMID: 28926237]
[24]
Soo, H.C.; Chung, F.F.; Lim, K.H.; Yap, V.A.; Bradshaw, T.D.; Hii, L.W.; Tan, S.H.; See, S.J.; Tan, Y.F.; Leong, C.O.; Mai, C.W.; Cudraflavone, C.; Cudraflavone, C. Induces tumor-specific apoptosis in colorectal cancer cells through inhibition of the phosphoinositide 3-kinase (PI3K)-AKT pathway. PLoS One, 2017, 12(1) e0170551
[http://dx.doi.org/10.1371/journal.pone.0170551] [PMID: 28107519]
[25]
Er, J.L.; Goh, P.N.; Lee, C.Y.; Tan, Y.J.; Hii, L.W.; Mai, C.W.; Chung, F.F.; Leong, C.O. Identification of inhibitors synergizing gemcitabine sensitivity in the squamous subtype of pancreatic ductal adenocarcinoma (PDAC). Apoptosis, 2018, 23(5-6), 343-355.
[http://dx.doi.org/10.1007/s10495-018-1459-6] [PMID: 29740790]

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