The novel curcumin derivative (1E,4Z,6E)-5-chloro-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one (5-chlorocurcumin) was prepared from natural curcumin. The newly synthesised compound was characterised by spectral studies (IR, 1H NMR, and 13C NMR). The free radical scavenging activity of 5-chlorocurcumin has been determined by measuring interaction with the stable free radical DPPH, and 5-chlorocurcumin has shown encouraging antioxidant activities. Theory calculations of the synthesised 5-chlorocurcumin were performed using molecular structures with optimised geometries. Molecular orbital calculations provided a detailed description of the orbitals, including spatial characteristics, nodal patterns, and the contributions of individual atoms. 1. Introduction Curcumin (1) [diferuloylmethane, 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-hepta-diene-3,5-dione] is a well-known acyclic diarylheptanoid identified as the major constituent of turmeric powder extracted from the rhizome of the plant Curcuma longa [1, 2]. Curcumin (1) has potent antioxidant activity [3–5] and has received attention as a promising nutraceutical or as a component of designer foods for its cancer preventive ability. With a unique conjugated structure including two methoxylated phenols and an enol β-diketone, curcumin shows a typical radical-trapping ability as a chain-breaking antioxidant. The antioxidant mechanism of curcumin and curcumin-related phenols has attracted significant attention [6–8], but it is still not well understood. In addition, curcumin blocks growth factor signaling via inhibition of tyrosine kinase activity or depletion of ErbB-2 [9]. More recently, it has been shown that curcumin causes cleavage of h-catenin, resulting in apoptosis in a colon cancer—derived cell line [10]. Antioxidant compounds play an important role as a health protecting factor. Scientific evidence suggests that antioxidants reduce the risk for chronic diseases including cancer and heart disease. Primary sources of naturally occurring antioxidants are whole grains, fruits, and vegetables. Plant sourced food antioxidants like vitamin C, vitamin E, carotenes, phenolic acids, phytate, and phytoestrogens have been recognized as having the potential to reduce disease risk. Most of the antioxidant compounds in a typical diet are derived from plant sources and belong to various classes of compounds with a wide variety of physical and chemical properties. Some compounds, such as gallates, have strong antioxidant activity, while others, such as the monophenols, are weak antioxidants [11]. For
References
[1]
A. M. Anderson, M. S. Mitchell, and R. S. Mohan, “Design, synthesis, biological evaluation and molecular docking of curcumin analogues as antioxidant,” Journal of Chemical Education, vol. 77, pp. 359–360, 2000.
[2]
V. Lampe, “Synthesis von curcumin,” Chemische Berichte, vol. 51, article 1347, 1918.
[3]
S. Sreejayan and M. N. A. Rao, “Nitric oxide scavenging by curcuminoids,” Journal of Pharmacy and Pharmacology, vol. 49, no. 1, pp. 105–107, 1997.
[4]
M. N. Kunchandy and A. Rao, “Oxygen radical scavenging activity of curcumin,” International Journal of Pharmaceutics, vol. 58, no. 3, pp. 237–240, 1990.
[5]
S. V. Jovanovic, C. W. Boone, S. Steenken, M. Trinoga, and R. B. Kaskey, “How curcumin works preferentially with water soluble antioxidants,” Journal of the American Chemical Society, vol. 123, no. 13, pp. 3064–3068, 2001.
[6]
G. J. Kelloff, J. A. Crowell, E. T. Hawk et al., “Clinical development plan: 9-cis-retinoic acid,” Journal of Cellular Biochemistry, vol. 26, pp. 158–167, 1996.
[7]
N. Noguchi, E. Komuro, E. Niki, and R. Willson, “Action if curcumin as antioxidant against lipid peroxidation,” Journal of Japan Oil Chemists' Society, vol. 43, pp. 1045–1051, 1994.
[8]
R. Hong, W. H. Spohn, and M. Hung, “Curcumin inhibits tyrosine kinase activity of p185(neu) and also depletes p185(neu1),” Clinical Cancer Research, vol. 5, no. 7, pp. 1884–1891, 1999.
[9]
A. S. Jaiswal, B. P. Marlow, N. Gupta, and S. Narayan, “β-catenin-mediated transactivation and cell—cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells,” Oncogene, vol. 21, no. 55, pp. 8414–8427, 2002.
[10]
F. T. Kolligs, M. T. Nieman, I. Winer et al., “ITF-2, a downstream target of the Wnt/TCF pathway, is activated in human cancers with β-catenin defects and promotes neoplastic transformation,” Cancer Cell, vol. 1, no. 2, pp. 144–155, 2002.
[11]
M. V. Kumaraswamy and S. Satish, “Antioxidant and anti-lipoxygenase activity of Thespesia lampas Dalz & Gibs,” Advances in Biological Research, vol. 2, no. 3-4, pp. 56–59, 2008.
[12]
N. Nenadis, O. Lazaridou, and M. Z. Tsimidou, “Use of reference compounds in antioxidant activity assessment,” Journal of Agricultural and Food Chemistry, vol. 55, no. 14, pp. 5452–5460, 2007.
[13]
N. F. Boyd and V. McGuire, “The possible role of lipid peroxidation in breast cancer risk,” Free Radical Biology and Medicine, vol. 10, no. 3-4, pp. 185–190, 1991.
[14]
R. L. Nelson, “Dietary iron and colorectal cancer risk,” Free Radical Biology and Medicine, vol. 12, no. 2, pp. 161–168, 1992.
[15]
P. Knekt, A. Reunanen, H. Takkunen, A. Aromaa, M. Heliovaara, and T. Hakulinen, “Body iron stores and risk of cancer,” International Journal of Cancer, vol. 56, no. 3, pp. 379–382, 1994.
[16]
G. S. Omenn, G. E. Goodman, M. D. Thornquist et al., “Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease,” The New England Journal of Medicine, vol. 334, no. 18, pp. 1150–1155, 1996.
[17]
R. A. Riemersma, D. A. Wood, C. C. A. Macintyre, R. A. Elton, K. F. Gey, and M. F. Oliver, “Risk of angina pectoris and plasma concentrations of vitamins A, C, and E and carotene,” The Lancet, vol. 337, no. 8732, pp. 1–5, 1991.
[18]
J. T. Salonen, K. Nyyssonen, H. Korpela, J. Tuomilehto, R. Seppanen, and R. Salonen, “High stored iron levels are associated with excess risk of myocardial infarction in Eastern Finnish men,” Circulation, vol. 86, no. 3, pp. 803–811, 1992.
[19]
D. A. Street, G. W. Comstock, R. M. Salkeld, W. Schüep, and M. J. Klag, “Serum antioxidants and myocardial infarction: are low levels of carotenoids and α-tocopherol risk factors for myocardial infarction?” Circulation, vol. 90, no. 3, pp. 1154–1161, 1994.
[20]
L. H. Kushi, A. R. Folsom, R. J. Prineas, P. J. Mink, Y. Wu, and R. M. Bostick, “Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women,” The New England Journal of Medicine, vol. 334, no. 18, pp. 1156–1162, 1996.
[21]
O. M. Panasenko, T. V. Vol'Nova, O. A. Azizova, and Y. A. Vladimirov, “Free radical modification of lipoproteins and cholesterol accumulation in cells upon atherosclerosis,” Free Radical Biology and Medicine, vol. 10, no. 2, pp. 137–148, 1991.
[22]
D. Steinberg, “Antioxidants and atherosclerosis. A current assessment,” Circulation, vol. 84, no. 3, pp. 1420–1425, 1991.
[23]
D. R. Janero, “Therapeutic potential of vitamin E in the pathogenesis of spontaneous atherosclerosis,” Free Radical Biology and Medicine, vol. 11, no. 1, pp. 129–144, 1991.
[24]
H. N. Hodis, W. J. Mack, L. LaBree et al., “Serial coronary angiographic evidence antioxidant vitamin intake reduces progression of coronary artery atherosclerosis,” Journal of the American Medical Association, vol. 273, no. 23, pp. 1849–1854, 1995.
[25]
K. Hensley, D. A. Butterfield, M. Mattson et al., “A model for β-amyloid aggregation and neurotoxicity based on the free radical generating capacity of the peptide: implications of “molecular shrapnel” for Alzheimer's disease,” Proceedings of the Western Pharmacology Society, vol. 38, pp. 113–120, 1995.
[26]
K. Hensley, J. M. Carney, M. P. Mattson et al., “A model for β-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 8, pp. 3270–3274, 1994.
[27]
D. A. Butterfield, L. Martin, J. M. Carney, and K. Hensley, “Aβ(25–35) peptide displays H2O2-like reactivity towards aqueous FE2+, nitroxide spin probes, ant synaptosomal membrane proteins,” Life Sciences, vol. 58, no. 3, pp. 217–228, 1995.
[28]
D. A. Butterfield, “β-amyloid-associated free radical oxidative stress and neurotoxicity: implications for Alzheimer's disease,” Chemical Research in Toxicology, vol. 10, no. 5, pp. 495–506, 1997.
[29]
R. Sultana and D. A. Butterfield, “Redox proteomics studies of in vivo amyloid beta-peptide animal models of Alzheimer's disease: insight into the role of oxidative stress,” Proteomics, vol. 2, no. 5, pp. 685–696, 2008.
[30]
C. Rice-Evans, C. Rice-Evans, B. Halliwell, and G. G. Lunt, Free Radicals and Oxidative Stress: Environment, Drugs and Food Additives, Portland Press, London, UK, 1995.
[31]
A. A. Al-Amiery, A. A. H. Kadhum, and A. B. Mohamad, “Antifungal and antioxidant activities of pyrrolidone thiosemicarbazone complexes,” Bioinorganic Chemistry and Applications, vol. 2012, Article ID 795812, 5 pages, 2012.
[32]
A. A. Al-Amiery, “Antimicrobial and antioxidant activities of new metal complexes derived from (E)-3-((5-phenyl-1,3,4-oxadiazol-2-ylimino)methyl)naphthalen-2-ol,” Medicinal Chemistry Research, vol. 21, pp. 3204–3213, 2012.
[33]
Y. Chen, M. Wang, R. T. Rosen, and C. Ho, “2,2-diphenyl-1-picrylhydrazyl radical-scavenging active components from Polygonum multiflorum Thunb,” Journal of Agricultural and Food Chemistry, vol. 47, no. 6, pp. 2226–2228, 1999.
[34]
A. A. Al-Amiery, Y. K. Al-Majedy, H. Abdulreazak, and H. Abood, “Synthesis, characterization, theoretical crystal structure, and antibacterial activities of some transition metal complexes of the thiosemicarbazone (Z)-2-(pyrrolidin-2-ylidene)hydrazinecarbothioamide,” Bioinorganic Chemistry and Applications, vol. 2011, Article ID 483101, 6 pages, 2011.
[35]
A. A. H. Kadhum, A. B. Mohamad, A. A. Al-Amiery, and M. S. Takriff, “Antimicrobial and antioxidant activities of new metal complexes derived from 3-aminocoumarin,” Molecules, vol. 16, no. 8, pp. 6969–6984, 2011.
[36]
A. A. Al-Amiery, A. Y. Musa, A. A. H. Kadhum, and A. B. Mohamad, “The use of umbelliferone in the synthesis of new heterocyclic compounds,” Molecules, vol. 16, no. 8, pp. 6833–6843, 2011.
[37]
A. A. H. Kadhum, A. A. Al-Amiery, M. Shikara, and A. Mohamad, “Synthesis, structure elucidation and DFT studies of new thiadiazoles,” International Journal of Physical Sciences, vol. 6, no. 29, pp. 6692–6697, 2012.
[38]
F. A. Hashem, “Investigation of free radical scavenging activity by ESR for coumarins isolated from Tecoma radicans,” Journal of Medical Sciences, vol. 7, no. 6, pp. 1027–1032, 2007.
[39]
G. Cao, E. Sofic, and R. L. Prior, “Antioxidant capacity of tea and common vegetables,” Journal of Agricultural and Food Chemistry, vol. 44, no. 11, pp. 3426–3431, 1996.
[40]
A. A. Al-Amiery, Y. K. Al-Majedy, H. H. Ibrahim, and A. A. Al-Tamimi, “Antioxidant, antimicrobial, and theoretical studies of the thiosemicarbazone derivative Schiff base 2-(2-imino-1- methylimidazolidin-4-ylidene) hydrazinecarbothioamide (IMHC),” Organic and Medicinal Chemistry Letters, vol. 2, article 4, 2012.
[41]
J. R. Soares, T. C. P. Dinis, A. P. Cunha, and L. M. Almeida, “Antioxidant activities of some extracts of Thymus zygis,” Free Radical Research, vol. 26, no. 5, pp. 469–478, 1997.
[42]
P. Duh, Y. Tu, and G. Yen, “Antioxidant activity of water extract of Harng Jyur (Chyrsanthemum morifolium Ramat),” Lebensmittel-Wissenschaft & Technologie, vol. 32, no. 5, pp. 269–277, 1999.
[43]
M. Leopoldini, N. Russo, and M. Toscano, “The molecular basis of working mechanism of natural polyphenolic antioxidants,” Food Chemistry, vol. 125, no. 2, pp. 288–306, 2011.
[44]
D. Mikulski, M. Szel？g, M. Molski, and R. Górniak, “Quantum-chemical study on the antioxidation mechanisms of trans-resveratrol reactions with free radicals in the gas phase, water and ethanol environment,” Journal of Molecular Structure, vol. 951, no. 1–3, pp. 37–48, 2010.
[45]
Y. Shang, Y. Qian, X. Liu et al., “Radical-scavenging activity and mechanism of resveratrol-oriented analogues: influence of the solvent, radical, and substitution,” Journal of Organic Chemistry, vol. 74, no. 14, pp. 5025–5031, 2009.
[46]
D. Huang, O. U. Boxin, and R. L. Prior, “The chemistry behind antioxidant capacity assays,” Journal of Agricultural and Food Chemistry, vol. 53, no. 6, pp. 1841–1856, 2005.
[47]
M. Ozgen, R. N. Reese, A. Z. Tulio, J. C. Scheerens, and A. R. Miller, “Modified 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) method to measure antioxidant capacity of selected small fruits and comparison to ferric reducing antioxidant power (FRAP) and 2,2′-diphenyl-1-picrylhydrazyl (DPPH) methods,” Journal of Agricultural and Food Chemistry, vol. 54, no. 4, pp. 1151–1157, 2006.
