Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Synthesis of Curcumin Glycosides with Enhanced Anticancer Properties Using One-Pot Multienzyme Glycosylation Technique

  • Gurung, Rit Bahadur (Department of Life Science and Biochemical Engineering, Sun Moon University) ;
  • Gong, So Youn (Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University) ;
  • Dhakal, Dipesh (Department of Life Science and Biochemical Engineering, Sun Moon University) ;
  • Le, Tuoi Thi (Department of Life Science and Biochemical Engineering, Sun Moon University) ;
  • Jung, Na Rae (Department of Life Science and Biochemical Engineering, Sun Moon University) ;
  • Jung, Hye Jin (Department of Life Science and Biochemical Engineering, Sun Moon University) ;
  • Oh, Tae Jin (Department of Life Science and Biochemical Engineering, Sun Moon University) ;
  • Sohng, Jae Kyung (Department of Life Science and Biochemical Engineering, Sun Moon University)
  • Received : 2017.01.19
  • Accepted : 2017.06.19
  • Published : 2017.09.28
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Abstract

Curcumin is a natural polyphenolic compound, widely acclaimed for its antioxidant, anti-inflammatory, 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-${\alpha}-{\text\tiny{D}}$-glucose or UDP-${\alpha}-{\text\tiny{D}}$-2-deoxyglucose as donor substrate were employed. The result indicated significant conversion of curcumin to its glycosylated derivatives: curcumin 4'-O-${\beta}$-glucoside, curcumin 4',4"-di-O-${\beta}$-glucoside, curcumin 4'-O-${\beta}$-2-deoxyglucoside, and curcumin 4',4"-di-O-${\beta}$-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-${\beta}$-glucoside and curcumin 4'-O-${\beta}$-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.

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References

  1. Gupta SC, Sung B, Kim JH, Prasad S, Li S, Aggarwal BB. 2013. Multitargetting by tumeric, the golden spice: from kitchen to clinic. Mol. Food Res. 57: 1510-1528. https://doi.org/10.1002/mnfr.201100741
  2. Ak T, Gulcin I. 2008. Antioxidant and radical scavenging properties of curcumin. Chem. Biol. Interact. 174: 27-37. https://doi.org/10.1016/j.cbi.2008.05.003
  3. Lal J, Gupta SK, Thavaselvam D, Agarwal DD. 2012. Design, synthesis, synergistic antimicrobial activity and cytotoxicity of 4-aryl substituted 3,4-dihydropyrimidinones of curcumin. Bioorg. Med. Chem. Lett. 22: 2872-2876. https://doi.org/10.1016/j.bmcl.2012.02.056
  4. Mishra S, Karmodiya K, Surolia N, Surolia A. 2008. Synthesis and exploration of novel curcumin analogues as anti-malarial agents. Bioorg. Med. Chem. 16: 2894-2902. https://doi.org/10.1016/j.bmc.2007.12.054
  5. Chainani-Wu N. 2003. Safety and anti-inflammatory activity of curcumin: a component of turmeric (Curcuma longa). Altern. Complement. Med. 9: 161-168. https://doi.org/10.1089/107555303321223035
  6. Singh RK, Rai D, Yadav D, Bhargava A, Balzarini J, De Clercq E. 2010. Synthesis, antibacterial and antiviral properties of curcumin bioconjugates bearing dipeptide, fatty acids and folic acid. Eur. J. Med. Chem. 45: 1078-1086. https://doi.org/10.1016/j.ejmech.2009.12.002
  7. Ruby AJ, Kuttan G, Babu KD, Rajasekharan KN, Kuttan R. 1995. Anti-tumour and antioxidant activity of natural curcuminoids. Cancer Lett. 94: 79-83. https://doi.org/10.1016/0304-3835(95)03827-J
  8. Aggarwal S, Takada Y, Singh S, Myers JN, Aggarwal BB. 2004. Inhibition of growth and survival of human head and neck squamous cell carcinoma cells by curcumin via modulation of nuclear factor-${\kappa}B$ signaling. Int. J. Cancer 111:679-692. https://doi.org/10.1002/ijc.20333
  9. Yano S, Terai M, Shimizu KL, Futagami Y, Horie S, Tsuchiya S, et al. 2000. Antiallergic activity of Curcuma longa. (II). Features of inhibitory actions on histamine release from mast cells. Nat. Med. (Tokyo) 54: 325-329.
  10. Girish C, Pradhan SC. 2012. Hepatoprotective activities of picroliv, curcumin, and ellagic acid compared to silymarin on carbon-tetrachloride-induced liver toxicity in mice. J. Pharmacol. Pharmacother. 3: 149-155.
  11. Trujillo J, Chirino YI, Molina-Jijon E, Andérica-Romero AC, Tapia E, Pedraza-Chaverri J. 2013. Renoprotective effect of the antioxidant curcumin: recent findings. Redox Biol. 1: 448-456. https://doi.org/10.1016/j.redox.2013.09.003
  12. Kim M, Kim Y. 2010. Hypocholesterolemic effects of curcumin via up-regulation of cholesterol 7a-hydroxylase in rats fed a high fat diet. Nutr. Res. Pract. 4: 191-195. https://doi.org/10.4162/nrp.2010.4.3.191
  13. Altenburg JD, Bieberich AA, Terry C, Harvey KA, Vanhorn JF, Xu Z, et al. 2011. 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: 149. https://doi.org/10.1186/1471-2407-11-149
  14. Du Q, Hu B, An HM, Shen KP, Xu L, Deng S, et al. 2013. Synergistic anticancer effects of curcumin and resveratrol in Hepa1-6 hepatocellular carcinoma cells. Oncol. Rep. 29: 1851-1858. https://doi.org/10.3892/or.2013.2310
  15. Sreenivasan S, Krishnakumar S. 2015. Synergistic effect of curcumin in combination with anticancer agents in human retinoblastoma cancer cells lines. Curr. Eye Res. 40: 1153-1165. https://doi.org/10.3109/02713683.2014.987870
  16. Guzzarlamudi S, Singh PK, Pawar VK, Singh Y, Sharma K, Paliwal SK, et al. 2016. Synergistic chemotherapeutic activity of curcumin bearing methoxypolyethylene glycol-g-linoleic acid based micelles on breast cancer cells. Nanosci. Nanotechnol. 16: 4180-4190. https://doi.org/10.1166/jnn.2016.11699
  17. Zlotogorski A, Dayan A, Dayan D, Chaushu G, Salo T, Vered M. 2013. Nutraceuticals as new treatment approaches for oral cancer - I: curcumin. Oral Oncol. 49: 187-191. https://doi.org/10.1016/j.oraloncology.2012.09.015
  18. Shehzad A, Lee J, Lee JS. 2013. Curcumin in various cancers. Biofactors 39: 56-68. https://doi.org/10.1002/biof.1068
  19. Perrone D, Ardito F, Giannatempo G, Dioguardi M, Troiano G, Lo Russo L, et al. 2015. Biological and therapeutic activities, and anticancer properties of curcumin. Exp. Ther. Med. 10: 1615-1623. https://doi.org/10.3892/etm.2015.2749
  20. Sandur SK, Pandey MK, Sung B, Ahn KS, Murakami A, Sethi G, et al. 2007. Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism. Carcinogenesis 28: 1765-1773. https://doi.org/10.1093/carcin/bgm123
  21. Somparn P, Phisalaphong C, Nakornchai S, Unchern S, Morales NP. Comparative antioxidant activities of curcumin and its demethoxy and hydrogenated derivatives. Biol. Pharm. Bull. 30: 74-78.
  22. Sugiyama Y, Kawakishi S, Osawa T. 1996. Involvement of the beta-diketone moiety in the antioxidative mechanism of tetrahydrocurcumin. Biochem. Pharmacol. 52: 519-525. https://doi.org/10.1016/0006-2952(96)00302-4
  23. Ahmad MZ, Alkahtani SA, Akhter S, Ahmad FJ, Ahmad J, Akhtar MS, et al. 2015. Progress in nanotechnology-based drug carrier in designing of curcumin nanomedicines for cancer therapy: current state-of-the-art. J. Drug Target. 11: 1-21.
  24. Wang YJ, Pan MH, Cheng AL, Lin LI, Ho YS, Hsieh CY, et al. 1997. Stability of curcumin in buffer solutions and characterization of its degradation products. J. Pharm. Biomed. Anal. 15: 1867-1876. https://doi.org/10.1016/S0731-7085(96)02024-9
  25. Anand P, Nair HB, Sung B, Kunnumakkara AB, Yadav VR, Tekmal RR, et al. 2010. Bioavailability of curcumin: problems and promises. Biochem. Pharmacol. 79: 330-338. https://doi.org/10.1016/j.bcp.2009.09.003
  26. Lian T, Peng M, Vermorken AJ, Jin Y, Luo Z, Van de Ven WJ, et al. 2016. Synthesis and characterization of curcuminfunctionalized HP-${\beta}$-CD-modified GoldMag nanoparticles as drug delivery agents. J. Nanosci. Nanotechnol. 16: 6258-6264. https://doi.org/10.1166/jnn.2016.11370
  27. Liang G, Shao L, Wang Y, Zhao C, Chu Y, Xiao J, et al. 2009. Exploration and synthesis of curcumin analogues with improved structural stability both in vitro and in vivo as cytotoxic agents. Bioorg. Med. Chem. 17: 2623-2631. https://doi.org/10.1016/j.bmc.2008.10.044
  28. Le TT, Pandey RP, Gurung RB, Dhakal D, Sohng JK. 2014. Efficient enzymatic systems for synthesis of novel ${\alpha}$-mangostin glycosides exhibiting antibacterial activity against grampositive bacteria. Appl. Microbiol. Biotechnol. 98: 8527-8538. https://doi.org/10.1007/s00253-014-5947-5
  29. Lepak A, Gutmann A, Kulmer ST, Nidetzky B. 2015. Creating a water-soluble resveratrol-based antioxidant by site-selective enzymatic glucosylation. ChemBioChem 16: 1870-1874. https://doi.org/10.1002/cbic.201500284
  30. Kaminaga Y, Nagatsu A, Akiyama T, Sugimoto N, Yamazaki T, Maitani T, et al. 2003. Molecular cloning and characterization of a glucosyltransferase catalyzing glucosylation of curcumin in cultured Catharanthus roseus cells. FEBS Lett. 555: 311-316. https://doi.org/10.1016/S0014-5793(03)01265-1
  31. Dhakal D, Le TT, Pandey RP, Jha AK, Gurung RB, Parajuli P, et al. 2015. Enhanced production of nargenicin A(1) and generation of novel glycosylated derivatives. Appl. Biochem. Biotechnol. 175: 2934-2949. https://doi.org/10.1007/s12010-014-1472-3
  32. Shin JY, Pandey RP, Jung HY, Chu LL, Park YI, Sohng JK. 2016. In vitro single-vessel enzymatic synthesis of novel Resvera-A glucosides. Carbohydr. Res. 424: 8-14. https://doi.org/10.1016/j.carres.2016.02.001
  33. Vijayakumar GR, Divakar S. 2005. Amyloglucosidase-catalysed synthesis of curcumin-bis-alpha-D-glucoside, a response surface methodology study. Biotechnol. Lett. 27: 1411-1415. https://doi.org/10.1007/s10529-005-3691-8
  34. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. 2007. Bioavailability of curcumin: problems and promises. Mol. Pharm. 4: 807-818. https://doi.org/10.1021/mp700113r
  35. Priyadarsini KI. 2013. Chemical and structural features influencing the biological activity of curcumin. Curr. Pharm. Des. 19: 2093-2100.
  36. Masada S, Kawase Y, Nagatoshi M, Oguchi Y, Terasaka K, Mizukami H. 2007. An efficient chemoenzymatic production of small molecule glucosides with in situ UDP-glucose recycling. FEBS Lett. 581: 2562-2566. https://doi.org/10.1016/j.febslet.2007.04.074
  37. Terasaka K, Misutani Y, Nagatsu A, Mizukami H. 2012. In situ UDP-glucose regeneration unravels diverse functions of plant secondary product glycosyltransferases. FEBS Lett. 586: 4344-4350. https://doi.org/10.1016/j.febslet.2012.10.045
  38. Mohri K, Watanabe Y, Yoshida Y, Satoh M, Isobe K, Suqimoto N, et al. 2003. Synthesis of glycosylcurcuminoids. Chem. Pharm. Bull. (Tokyo) 51: 1268-1272. https://doi.org/10.1248/cpb.51.1268
  39. Masada S, Kawase Y, Nagatoshi M, Oguchi Y, Terasaka K, Mizukami H. 2007. An efficient chemoenzymatic production of small molecule glucosides with in situ UDP-glucose recycling. FEBS Lett. 581: 2562-2566. https://doi.org/10.1016/j.febslet.2007.04.074
  40. Bubb WA. 2003. NMR spectroscopy in the study of carbohydrates: characterizing the structural complexity, pp. 1-19. In Traficante DD (ed.), Concepts in Magnetic Resonance Part A, Vol. 19A. John Wiley & Sons, Inc., New Jersey.
  41. Amann S, Drager G, Rupprath C, Kirschning A, Elling L. 2001. (Chemo)enzymatic synthesis of dTDP-activated 2,6- dideoxysugars as building blocks of polyketide antibiotics. Carbohydr. Res. 335: 23-32. https://doi.org/10.1016/S0008-6215(01)00195-1
  42. Oh J, Lee SG, Kim BG, Sohng JK, Liou KK, Lee HC. 2003. One-pot enzymatic production of dTDP-4-keto-6-deoxy-Dglucose from dTMP and glucose-1-phosphate. Biotechnol. Bioeng. 84: 452-458. https://doi.org/10.1002/bit.10789
  43. Kaminaga Y, Sahin FP, Mizukami H. 2004. Molecular cloning and characterization of a glucosyltransferase catalyzing glucosylation of curcumin in cultured Catharanthus roseus cells. FEBS Lett. 567: 197-202. https://doi.org/10.1016/j.febslet.2004.04.056
  44. Crespy V, Morand C, Besson C, Manach C, Demigne C, Remesy C. 2001. Comparison of the intestinal absorption of quercetin, phloretin and their glucosides in rats. J. Nutr. 131: 2109-2114. https://doi.org/10.1093/jn/131.8.2109
  45. Parvathy KS, Negi PS, Srinivas P. 2009. Antioxidant, antimutagenic and antibacterial activities of curcumin-${\beta}$-diglucoside. Food Chem. 115: 265-271. https://doi.org/10.1016/j.foodchem.2008.12.036
  46. Gunes H, Gulen D, Mutlu R, Gumus A, Tas T, Topkaya AE. 2013. Antibacterial effects of curcumin: an in vitro minimum inhibitory concentration study. Toxicol. Ind. Health 32: 246-250.
  47. Mun SH, Joung DK, Kim SH, Kang OH, Kim SB, Seo YS, et al. 2013. Synergistic antibacterial effect of curcumin against methicillin-resistant Staphylococcus aureus. Phytomedicine 20: 714-718. https://doi.org/10.1016/j.phymed.2013.02.006
  48. Moghadamtousi SZ, Kadir HA, Hassandarvish P, Tajik H, Abubakar S, Zandi K. 2014. A review on antibacterial, antiviral, and antifungal activity of curcumin. Biomed. Res. Int. 2014: 12.
  49. Kapoor N, Narain U, Misra K. 2007. Bioactive conjugates of curcumin having ester, peptide, thiol and disulphide links. J. Sci. Ind. Res. 66: 647-650.
  50. Prasad E, Hameeda B, Rao AB, Reddy G. 2014. Biotransformation of curcumin for improved biological activity and antiproliferative activity on acute HT-29 human cell lines. Indian J. Biotechnol. 13: 324-329.
  51. Rai D, Singh JK, Roy N, Panda D. 2008. Curcumin inhibits FtsZ assembly: an attractive mechanism for its antibacterial activity. Biochem. J. 410: 147-155. https://doi.org/10.1042/BJ20070891
  52. Yun DG, Lee DG. Antibacterial activity of curcumin via apoptosis-like response in Escherichia coli. Appl. Microbiol. Biotechnol. 100: 5505-5514.
  53. Lombo F, Olano C, Salas JA, Mendez C. 2009. Sugar biosynthesis and modification, pp. 277-308. In Abelson JN, Simon MI (eds.), Methods in Enzymology. Academic Press, San Diego.
  54. Wilken R, Veena MS, Wang MB, Srivatsan ES. 2011. Curcumin: a review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol. Cancer 10: 12. https://doi.org/10.1186/1476-4598-10-12
  55. Chen CC, Sureshbabul M, Chen HW, Lin YS, Lee JY, Hong QS, et al. 2013. Curcumin suppresses metastasis via Sp-1, FAK inhibition, and E-cadherin upregulation in colorectal cancer. Evid. Based Complement. Alternat. Med. 2013: 541695.
  56. Monks A, Scudiero D, Skehan P, Shoemaker R, Paull K, Vistica D, et al. 1991. Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J. Natl. Cancer Inst. 83: 757-766. https://doi.org/10.1093/jnci/83.11.757
  57. Langenhan JM, Peters NR, Guzei IA, Hoffmann FM, Thorson JS. 2005. Enhancing the anticancer properties of cardiac glycosides by neoglycorandomization. Proc. Natl. Acad. Sci. USA 102: 12305-12310. https://doi.org/10.1073/pnas.0503270102
  58. Ahmed A, Peters NR, Fitzgerald MK, Watson JA, Hoffmann FM, Thorson JS. 2006. Colchicine glycorandomization influences cytotoxicity and mechanism of action. J. Am. Chem. Soc. 128: 14224-14225. https://doi.org/10.1021/ja064686s
  59. Dhakal D, Sohng JK. 2015. Commentary: toward a new focus in antibiotic and drug discovery from the Streptomyces arsenal. Front. Microbiol. 6: 727.
  60. Dhakal D, Sohng JK. 2017. Coalition of biology and chemistry for ameliorating antimicrobial drug discovery. Front. Microbiol. 8: 734. https://doi.org/10.3389/fmicb.2017.00734

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