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Synthesis of α-cichoriin Using Deinococcus geothermalis Amylosucrase and Its Antiproliferative Effect

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초록

Glycosylation of aesculetin was performed using amylosucrase from the hyperthermophilic bacterium Deinococcus geothermalis DSM 11300 to improve the solubility and biological activity of aesculetin. A newly synthesized aesculetin glycoside was identified as α-cichoriin (aesculetin 7-α-D-glucoside) by nuclear magnetic resonance analysis. The solubility of α-cichoriin was 11 times higher than that of aesculetin because of the attached glucose moiety. Aesculetin and α-cichoriin had no significant effect on the proliferation of normal cells, such as RAW 264.7, but they showed a cell proliferation inhibitory effect on B16F10 melanoma cells. Unlike treatment with aesculetin and α-cichoriin, aesculin (aesculetin 6-β-D-glucoside) showed no antiproliferative activity in B16F10 cells. Based on the molecular structures of aesculin and α- cichoriin, the position where glucose binds to aesculetin and the anomeric configuration between glucose and aesculetin are thought to be important for exerting an antiproliferative effect on the B16F10 cell line. Based on these results, we propose that α-cichoriin, the α-glycosylated form of aesculetin, may serve as a model for developing phytochemical analogs with therapeutic potential for the treatment of diseases associated with tumor cell proliferation without cytotoxicity to normal cells.

Abstract

Glycosylation of aesculetin was performed using amylosucrase from the hyperthermophilic bacterium Deinococcus geothermalis DSM 11300 to improve the solubility and biological activity of aesculetin. A newly synthesized aesculetin glycoside was identified as α-cichoriin (aesculetin 7-α-D-glucoside) by nuclear magnetic resonance analysis. The solubility of α-cichoriin was 11 times higher than that of aesculetin because of the attached glucose moiety. Aesculetin and α-cichoriin had no significant effect on the proliferation of normal cells, such as RAW 264.7, but they showed a cell proliferation inhibitory effect on B16F10 melanoma cells. Unlike treatment with aesculetin and α-cichoriin, aesculin (aesculetin 6-β-D-glucoside) showed no antiproliferative activity in B16F10 cells. Based on the molecular structures of aesculin and α- cichoriin, the position where glucose binds to aesculetin and the anomeric configuration between glucose and aesculetin are thought to be important for exerting an antiproliferative effect on the B16F10 cell line. Based on these results, we propose that α-cichoriin, the α-glycosylated form of aesculetin, may serve as a model for developing phytochemical analogs with therapeutic potential for the treatment of diseases associated with tumor cell proliferation without cytotoxicity to normal cells.

참고문헌 (46)

  1. Liang C, "Pharmacological activities and synthesis of esculetin and its derivatives : A minireview", Molecules, 22, pp.387~ (2017)
  2. Kaneko T, "Inhibitory effect of natural coumarin compounds, esculetin and esculin, on oxidative DNA damage and formation of aberrant crypt foci and tumors induced by 1, 2-dimethylhydrazine in rat colons", Biol. Pharm. Bull, 30, pp.2052~2057 (2007)
  3. Marinova EM, "Antioxidative action of the ethanolic extract and some hydroxycoumarins of Fraxinus ornus bark", Food Chem, 51, pp.125~132 (1994)
  4. Fylakatakidou KC, "Natural and synthetic coumarin derivatives with antiinflammatory", antioxidant activities, 2004, pp.10, 3813~3833
  5. Riveiro ME, "Coumarins : old compounds with novel, promising therapeutic perspectives", Curr. Med. Chem, 17, pp.1325~1338 (2010)
  6. Chu CY, "Induction of apoptosis by esculetin in human leukemia cells", Eur. J. Pharmacol, 416, pp.25~32 (2001)
  7. Pan L, "Esculetin inhibits Ras-mediated cell proliferation and attenuates vascular restenosis following angioplasty in rats", Biochem. Pharmacol, 65, pp.1897~1905 (2003)
  8. Finn GJ, "In vitro cytotoxic potential and mechanism of action of selected coumarins, using human renal cell lines", Cancer Lett, 183, pp.61~68 (2002)
  9. Kawaii S, "The antiproliferative effect of coumarins on several cancer cell lines", Anticancer Res, 21, pp.917~924 (2001)
  10. Kawase M, "Structure-cytotoxic activity relationships of simple hydroxylated coumarins", Anticancer Res, 23, pp.3243~3246 (2003)
  11. Lacy A, "Studies on coumarins and coumarinrelated compounds to determine their therapeutic role in the treatment of cancer", Curr. Pharm. Des, 10, pp.3797~3811 (2004)
  12. Al-Akhras MAH, "Introducing Cichorium Pumilum as a potential therapeutical agent against drug-induced benign breast tumor in rats", Electromagn. Biol. Med, 31, pp.299~309 (2012)
  13. 박소윤, "Synthesis of Aesculetin and Aesculin Glycosides Using Engineered Escherichia coli Expressing Neisseria polysaccharea Amylosucrase", Journal of Microbiology and Biotechnology, 28(4), pp.566~570 (2018), 한국미생물·생명공학회
  14. Liang SC, "Identification and characterization of human UDP-glucuronosyltransferases responsible for the in vitro glucuronidation of daphnetin", Drug Metab. Dispos, 38, pp.973~980 (2010)
  15. Xia YL, "Identification and characterization of human UDP-glucuronosyltransferases responsible for the glucuronidation of fraxetin", Drug Metab. Pharmacokinet, 29, pp.135~140 (2014)
  16. Zhang SF, "Improved synthesis technics of 6, 7-dimethoxy coumarin", J. Hebei Univ. Sci. Technol, 28, pp.24~25 (2007)
  17. Bull JA, "Application of the BHQ benzannulation reaction to the synthesis of benzo-fused coumarins", Tetrahedron Lett, 50, pp.3617~3620 (2009)
  18. Nemoto T, "Enantioselective total syntheses of(+)-decursin and related natural compounds using catalytic asymmetric epoxidation of an enon", Tetrahedron, 59, pp.6889~6897 (2003)
  19. Lim EK, "Plant glycosyltransferases : their potential as novel biocatalysts", Chem. Eur. J, 11, pp.5486~5494 (2005)
  20. Dürr C, "The glycosyltransferase UrdGT2 catalyzes both C-and O-glycosidic sugar transfers", Angew. Chem. Int. Ed, 43, pp.2962~2965 (2004)
  21. Hao B, "Biosynthesis of natural and novel C-glycosylflavones utilizing recombinant Oryza sativa C-glycosyltransferase(OsCGT)and Desmodium incanum root proteins", Phytochemistry, 125, pp.73~87 (2016)
  22. Wang X, "Molecular characterization of the C-glucosylation for puerarin biosynthesis in Pueraria lobata", Plant J, 90, pp.535~546 (2017)
  23. Ito T, "C-Glycosyltransferases catalyzing the formation of di-C-glucosyl flavonoids in citrus plants", Plant J, 91, pp.187~198 (2017)
  24. Chen D, "Probing the catalytic promiscuity of a regio-and stereospecific C-glycosyltransferase from Mangifera indica", J. Angew. Chem. Int. Ed, 54, pp.12678~12682 (2015)
  25. Chen D, "Enzymatic synthesis of acylphloroglucinol 3-C-glucosides from 2-O-glucosides using a C-glycosyltransferase from Mangifera indica", Chem. Eur. J, 22, pp.5873~5877 (2016)
  26. Hoffmeister D, "The C-glycosyltransferase UrdGT2 is unselective toward D-and Lconfigured nucleotide-bound rhodinoses", J. Am. Chem. Soc, 125, pp.4678~4679 (2003)
  27. Andersen-Ranberg J, "Synthesis of C-glucosylated octaketide anthraquinones in Nicotiana benthamiana by using a multispecies-based biosynthetic pathway", ChemBioChem, 18, pp.1893~1897 (2017)
  28. Salem SM, "Two cooperative glycosyltransferases are responsible for the sugar diversity of saquayamycins isolated from Streptomyces sp. KY 40-1", ACS Chem. Biol, 12, pp.2529~2534 (2017)
  29. 서동호, "Versatile biotechnological applications of amylosucrase, a novel glucosyltransferase", Food Science and Biotechnology, 29(1), pp.1~16 (2020), 한국식품과학회[DOI]
  30. Chiang C-M, "Production of new isoflavone diglucosides from glycosylation of 8-hydroxydaidzein by Deinococcus geothermalis amylosucrase", Fermentation, 7, pp.232~ (2021)
  31. Rha CS, "Using amylosucrase for the controlled synthesis of novel isoquercitrin glycosides with different glycosidic linkages", J. Agric. Food Chem, 68, pp.13798~13805 (2020)
  32. Rha CS, "Simple and efficient production of highly soluble daidzin glycosides by amylosucrase from Deinococcus geothermalis", J. Agric. Food Chem, 67, pp.12824~12832 (2019)
  33. Cho HK, "Biosynthesis of(+)-catechin glycosides using recombinant amylosucrase from Deinococcus geothermalis DSM 11300", Enzyme Microb. Technol, 49, pp.246~253 (2011)
  34. Moon YH, "Synthesis, structure analyses, and characterization of novel epigallocatechin gallate(EGCG)glycosides using the glucansucrase from Leuconostoc mesenteroides B-1299CB", J. Agric. Food Chem, 54, pp.1230~1237 (2006)
  35. Lee SJ, "Transglycosylation of naringin by Bacillus stearothermophilus maltogenic amylase to give glycosylated naringin", J. Agric. Food Chem, 47, pp.3669~3674 (1999)
  36. 고진아, "Enzymatic Synthesis of Puerarin Glucosides Using Leuconostoc Dextransucrase", Journal of Microbiology and Biotechnology, 22(9), pp.1224~1229 (2012), 한국미생물·생명공학회[DOI]
  37. Moon YH, "Synthesis and characterization of novel quercetin-α-D-glucopyranosides using glucansucrase from Leuconostoc mesenteroides", Enzyme Microb. Technol, 40, pp.1124~1129 (2007)
  38. Acero JL, "Oxidation of esculetin, a model pollutant present in cork processing wastewaters, by chemical methods", Ozone : Sci. Eng, 27, pp.317~326 (2005)
  39. Hollman PC, "The sugar moiety is a major determinant of the absorption of dietary flavonoid glycosides in man", Free Radic. Res, 32, pp.569~573 (1999)
  40. Jiang JR, "Conversion of puerarin into its 7-O-glycoside derivatives by Microbacterium oxydans(CGMCC 1788)to improve its water solubility and pharmacokinetic properties", Appl. Microbiol. Biotechnol, 81, pp.647~657 (2008)
  41. Yamada M, "Bioavailability of glucosyl hesperidin in rats", Biosci. Biotechnol. Biochem, 70, pp.1386~1394 (2006)
  42. Marshall ME, "Phase I evaluation of coumarin(1, 2-benzopyrone)and cimetidine in patients with advanced malignancies", Mol. Biother, 3, pp.170~178 (1991)
  43. Mohler JL, "Phase II evaluation of coumarin(1, 2-benzopyrone)in metastatic prostatic carcinoma", Prostate, 20, pp.123~131 (1992)
  44. Thornes RD, "Treatment with coumarin to prevent or delay recurrence of malignant melanoma", J. Cancer Res. Clin. Oncol, 120, pp.32~34 (1994)
  45. Egan D, "The pharmacology, metabolism, analysis, and applications of coumarin and coumarin-related compounds", Drug Metab. Res, 22, pp.503~529 (1990)
  46. Funayama M, "Effects of α-and β-Arbutin on activity of tyrosinases from mushroom and mouse melanoma", Biosci. Biotech. Biochem, 59, pp.143~144 (1995)

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