Synthesis of Curcumin Glycosides with Enhanced Anticancer Properties Using One-Pot Multienzyme Glycosylation Technique
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Curcumin is a natural polyphenolic compound, widely acclaimed for its antioxidant, antiinflammatory, antibacterial, and anticancerous properties. However, its use has been limited due to its low-aqueous solubility and poor bioavailability, rapid clearance, and low cellular uptake. In order to assess the effect of glycosylation on the pharmacological properties of curcumin, one-pot multienzyme (OPME) chemoenzymatic glycosylation reactions with UDP- α-D-glucose or UDP-α-D-2-deoxyglucose as donor substrate were employed. The result indicated significant conversion of curcumin to its glycosylated derivatives: curcumin 4’-O-β- glucoside, curcumin 4’,4’’-di-O-β-glucoside, curcumin 4’-O-β-2-deoxyglucoside, and curcumin 4’,4’’-di-O-β-2-deoxyglucoside. The products were characterized by ultra-fast performance liquid chromatography, high-resolution quadruple-time-of-flight electrospray ionization-mass spectrometry, and NMR analyses. All the products showed improved water solubility and comparable antibacterial activities. Additionally, the curcumin 4’-O-β-glucoside and curcumin 4’-O-β-2-deoxyglucoside showed enhanced anticancer activities compared with the parent aglycone and diglycoside derivatives. This result indicates that glycosylation can be an effective approach for enhancing the pharmaceutical properties of different natural products, such as curcumin.
Abstract
Curcumin is a natural polyphenolic compound, widely acclaimed for its antioxidant, antiinflammatory, antibacterial, and anticancerous properties. However, its use has been limited due to its low-aqueous solubility and poor bioavailability, rapid clearance, and low cellular uptake. In order to assess the effect of glycosylation on the pharmacological properties of curcumin, one-pot multienzyme (OPME) chemoenzymatic glycosylation reactions with UDP- α-D-glucose or UDP-α-D-2-deoxyglucose as donor substrate were employed. The result indicated significant conversion of curcumin to its glycosylated derivatives: curcumin 4’-O-β- glucoside, curcumin 4’,4’’-di-O-β-glucoside, curcumin 4’-O-β-2-deoxyglucoside, and curcumin 4’,4’’-di-O-β-2-deoxyglucoside. The products were characterized by ultra-fast performance liquid chromatography, high-resolution quadruple-time-of-flight electrospray ionization-mass spectrometry, and NMR analyses. All the products showed improved water solubility and comparable antibacterial activities. Additionally, the curcumin 4’-O-β-glucoside and curcumin 4’-O-β-2-deoxyglucoside showed enhanced anticancer activities compared with the parent aglycone and diglycoside derivatives. This result indicates that glycosylation can be an effective approach for enhancing the pharmaceutical properties of different natural products, such as curcumin.
참고문헌 (60)
- Gupta SC, "Multitargetting by tumeric, the golden spice: from kitchen to clinic", Mol. Food Res, 57, pp.1510~1528 (2013)
- Ak T, "Antioxidant and radical scavenging properties of curcumin", Chem. Biol. Interact, 174, pp.27~37 (2008)
- Lal J, "Design, synthesis, synergistic antimicrobial activity and cytotoxicity of 4-aryl substituted 3,4-dihydropyrimidinones of curcumin", Bioorg. Med. Chem. Lett, 22, pp.2872~2876 (2012)
- Mishra S, "Synthesis and exploration of novel curcumin analogues as anti-malarial agents", Bioorg. Med. Chem, 16, pp.2894~2902 (2008)
- Chainani-Wu N., "Safety and anti-inflammatory activity of curcumin: a component of turmeric (Curcuma longa)", Altern. Complement. Med, 9, pp.161~168 (2003)
- Singh RK, "Synthesis, antibacterial and antiviral properties of curcumin bioconjugates bearing dipeptide, fatty acids and folic acid", Eur. J. Med. Chem, 45, pp.1078~1086 (2010)
- Ruby AJ, "Anti-tumour and antioxidant activity of natural curcuminoids", Cancer Lett, 94, pp.79~83 (1995)
- Aggarwal S, "Inhibition of growth and survival of human head and neck squamous cell carcinoma cells by curcumin via modulation of nuclear factor-κB signaling", Int. J. Cancer, 111, pp.679~692 (2004)
- Yano S, "Antiallergic activity of Curcuma longa. (II). Features of inhibitory actions on histamine release from mast cells", Nat. Med, 54, pp.325~329 (2000)
- Girish C, "Hepatoprotective activities of picroliv, curcumin, and ellagic acid compared to silymarin on carbon-tetrachloride-induced liver toxicity in mice", J. Pharmacol. Pharmacother, 3, pp.149~155 (2012)
- Trujillo J, "Renoprotective effect of the antioxidant curcumin: recent findings", Redox Biol, 1, pp.448~456 (2013)
- 김민지, "Hypocholesterolemic effects of curcumin via up-regulation of cholesterol 7a-hydroxylase in rats fed a high fat diet", Nutrition Research and Practice, 4(3), pp.191~195 (2010), 한국영양학회
- Altenburg JD, "A synergistic antiproliferation effect of curcumin and docosahexaenoic acid in SK-BR-3 breast cancer cells: unique signaling not explained by the effects of either compound alone", BMC Cancer, 11, pp.149~ (2011)
- Du Q, "Synergistic anticancer effects of curcumin and resveratrol in Hepa1-6 hepatocellular carcinoma cells", Oncol. Rep, 29, pp.1851~1858 (2013)
- Sreenivasan S, "Synergistic effect of curcumin in combination with anticancer agents in human retinoblastoma cancer cells lines", Curr. Eye Res, 40, pp.1153~1165 (2015)
- Guzzarlamudi S, "Synergistic chemotherapeutic activity of curcumin bearing methoxypolyethylene glycol-g-linoleic acid based micelles on breast cancer cells", Nanosci. Nanotechnol, 16, pp.4180~4190 (2016)
- Zlotogorski A, "Nutraceuticals as new treatment approaches for oral cancer – I: curcumin", Oral Oncol, 49, pp.187~191 (2013)
- Shehzad A, "Curcumin in various cancers", Biofactors, 39, pp.56~68 (2013)
- Perrone D, "Biological and therapeutic activities, and anticancer properties of curcumin", Exp. Ther. Med, 10, pp.1615~1623 (2015)
- Sandur SK, "Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism", Carcinogenesis, 28, pp.1765~1773 (2007)
- Somparn P, "Comparative antioxidant activities of curcumin and its demethoxy and hydrogenated derivatives", Biol. Pharm. Bull, 30, pp.74~78
- Sugiyama Y, "Involvement of the beta-diketone moiety in the antioxidative mechanism of tetrahydrocurcumin", Biochem. Pharmacol, 52, pp.519~525 (1996)
- Ahmad MZ, "Progress in nanotechnology-based drug carrier in designing of curcumin nanomedicines for cancer therapy: current state-of-the-art", J. Drug Target, 11, pp.1~21 (2015)
- Wang YJ, "Stability of curcumin in buffer solutions and characterization of its degradation products", J. Pharm. Biomed. Anal, 15, pp.1867~1876 (1997)
- Anand P, "Bioavailability of curcumin: problems and promises", Biochem. Pharmacol, 79, pp.330~338 (2010)
- Lian T, "Synthesis and characterization of curcuminfunctionalized HP-β-CD-modified GoldMag nanoparticles as drug delivery agents", J. Nanosci. Nanotechnol, 16, pp.6258~6264 (2016)
- Liang G, "Exploration and synthesis of curcumin analogues with improved structural stability both in vitro and in vivo as cytotoxic agents", Bioorg. Med. Chem, 17, pp.2623~2631 (2009)
- Le TT, "Efficient enzymatic systems for synthesis of novel α-mangostin glycosides exhibiting antibacterial activity against grampositive bacteria", Appl. Microbiol. Biotechnol, 98, pp.8527~8538 (2014)
- Lepak A, "Creating a water-soluble resveratrol-based antioxidant by site-selective enzymatic glucosylation", ChemBioChem, 16, pp.1870~1874 (2015)
- Kaminaga Y, "Molecular cloning and characterization of a glucosyltransferase catalyzing glucosylation of curcumin in cultured Catharanthus roseus cells", FEBS Lett, 555, pp.311~316 (2003)
- Dhakal D, "Enhanced production of nargenicin A(1) and generation of novel glycosylated derivatives", Appl. Biochem. Biotechnol, 175, pp.2934~2949 (2015)
- Shin JY, "In vitro single-vessel enzymatic synthesis of novel Resvera-A glucosides", Carbohydr. Res, 424, pp.8~14 (2016)
- Vijayakumar GR, "Amyloglucosidase-catalysed synthesis of curcumin-bis-alpha-D-glucoside, a response surface methodology study", Biotechnol. Lett, 27, pp.1411~1415 (2005)
- Anand P, "Bioavailability of curcumin: problems and promises", Mol. Pharm, 4, pp.807~818 (2007)
- Priyadarsini KI., "Chemical and structural features influencing the biological activity of curcumin", Curr. Pharm. Des, 19, pp.2093~2100 (2013)
- Masada S, "An efficient chemoenzymatic production of small molecule glucosides with in situ UDP-glucose recycling", FEBS Lett, 581, pp.2562~2566 (2007)
- Terasaka K, "In situ UDP-glucose regeneration unravels diverse functions of plant secondary product glycosyltransferases", FEBS Lett, 586, pp.4344~4350 (2012)
- Mohri K, "Synthesis of glycosylcurcuminoids", Chem. Pharm. Bull, 51, pp.1268~1272 (2003)
- Masada S, "An efficient chemoenzymatic production of small molecule glucosides with in situ UDP-glucose recycling", FEBS Lett, 581, pp.2562~2566 (2007)
- Bubb WA, "Concepts in Magnetic Resonance Part A, Vol. 19A", pp.1~19 (2003), John Wiley & Sons, Inc
- Amann S, "(Chemo)enzymatic synthesis of dTDP-activated 2,6-dideoxysugars as building blocks of polyketide antibiotics", Carbohydr. Res, 335, pp.23~32 (2001)
- Oh J, "One-pot enzymatic production of dTDP-4-keto-6-deoxy-Dglucose from dTMP and glucose-1-phosphate", Biotechnol. Bioeng, 84, pp.452~458 (2003)
- Kaminaga Y, "Molecular cloning and characterization of a glucosyltransferase catalyzing glucosylation of curcumin in cultured Catharanthus roseus cells", FEBS Lett, 567, pp.197~202 (2004)
- Crespy V, "Comparison of the intestinal absorption of quercetin, phloretin and their glucosides in rats", J. Nutr, 131, pp.2109~2114 (2001)
- Parvathy KS, "Antioxidant, antimutagenic and antibacterial activities of curcumin-β-diglucoside", Food Chem, 115, pp.265~271 (2009)
- Gunes H, "Antibacterial effects of curcumin: an in vitro minimum inhibitory concentration study", Toxicol. Ind. Health, 32, pp.246~250 (2013)
- Mun SH, "Synergistic antibacterial effect of curcumin against methicillin-resistant Staphylococcus aureus", Phytomedicine, 20, pp.714~718 (2013)
- Moghadamtousi SZ, "A review on antibacterial, antiviral, and antifungal activity of curcumin", Biomed. Res. Int, 2014, pp.12~ (2014)
- Kapoor N, "Bioactive conjugates of curcumin having ester, peptide, thiol and disulphide links", J. Sci. Ind. Res, 66, pp.647~650 (2007)
- Prasad E, "Biotransformation of curcumin for improved biological activity and antiproliferative activity on acute HT-29 human cell lines", Indian J. Biotechnol, 13, pp.324~329 (2014)
- Rai D, "Curcumin inhibits FtsZ assembly: an attractive mechanism for its antibacterial activity", Biochem. J, 410, pp.147~155 (2008)
- Yun DG, "Antibacterial activity of curcumin via apoptosis-like response in Escherichia coli", Appl. Microbiol. Biotechnol, 100, pp.5505~5514
- Lombó F, "Methods in Enzymology", pp.277~308 (2009), Academic Press
- Wilken R, "Curcumin:a review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma", Mol. Cancer, 10, pp.12~ (2011)
- Chen CC, "Curcumin suppresses metastasis via Sp-1, FAK inhibition, and E-cadherin upregulation in colorectal cancer", Evid. Based Complement. Alternat. Med, 2013, pp.541695~ (2013)
- Monks A, "Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines", J. Natl. Cancer Inst, 83, pp.757~766 (1991)
- Langenhan JM, "Enhancing the anticancer properties of cardiac glycosides by neoglycorandomization", Proc. Natl. Acad. Sci. USA, 102, pp.12305~12310 (2005)
- Ahmed A, "Colchicine glycorandomization influences cytotoxicity and mechanism of action", J. Am. Chem. Soc, 128, pp.14224~14225 (2006)
- Dhakal D, "Commentary: toward a new focus in antibiotic and drug discovery from the Streptomyces arsenal", Front. Microbiol, 6, pp.727~ (2015)
- Dhakal D, "Coalition of biology and chemistry for ameliorating antimicrobial drug discovery", Front. Microbiol, 8, pp.734~ (2017)
