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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

Reynoutria Japonica from Traditional Chinese Medicine: A Source of Competitive Adenosine Deaminase Inhibitors for Anticancer

Author(s): Xin-guo Zhang*, Guo-Yan Ma, Fei Kou, Wen-Jie Liu, Qiao-Yun Sun, Guang-Jun Guo, Xiao-Di Ma, Si-Jia Guo and Zhu Jian-Ning

Volume 22, Issue 2, 2019

Page: [113 - 122] Pages: 10

DOI: 10.2174/1386207322666190415100618

Price: $65

Abstract

Background: Adenosine deaminase (ADA) is an important enzyme in purine metabolism and is known as a potential therapeutic target for the treatment of lymphoproliferative disorders and cancer. Traditional Chinese Herbal Medicine (TCHM) is widely used alone or in combination with chemotherapy to treat cancer, due to its ability to deliver a broad variety of bioactive secondary metabolites as promising sources of novel organic natural agents.

Objective: In the present study, 29 varieties of medicinal plants were screened for the presence of ADA inhibitors.

Results: Extracts from Reynoutria japonica, Glycyrrhiza uralensis, Lithospermum erythrorhizon, Magnolia officinalis, Gardenia jasminoides, Stephania tetrandra, Commiphora myrrha, Raphanus sativus and Corydalis yanhusuo demonstrated strong ADA inhibition with rates greater than 50%. However, Reynoutria japonica possessed the highest ADA inhibitory activity at 95.26% and so was used in our study for isolating the ADA inhibitor to be further studied. Eight compounds were obtained and their structures were identified. The compound H1 had strong ADA inhibitory activity and was deduced to be emodin by 1H and 13C-NMR spectroscopic analysis with an IC50 of 0.629 mM. The molecular docking data showed that emodin could bind tightly to the active site of ADA. Our results demonstrated that emodin displayed a new biological activity which is ADA inhibitory activity with high cytotoxic activity against K562 leukemia cells. The bioactivity of cordycepin was significantly increased when used in combination with emodin.

Conclusion: Emodin may represent a good candidate anti-cancer therapy and adenosine protective agent.

Keywords: ADA inhibitors, Reynoutria japonica, cordycepin, lymphoproliferative disorders, anti-cancer therapy, traditional chinese medicine.

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[1]
Martinez, J.H. Additional insights into the structure and function of adenosine deaminase., Diss. Rice University 1998, Available at. http://hdl.handle.net/1911/19286
[2]
Conway, E.J.; Cooke, R. The deaminase of adenosine and adenylic acid in blood and tissues. Biochem. J., 1939, 33(4), 479-492.
[3]
Gillerman, I.; Fischer, B. Investigations into the origin of the molecular recognition of several adenosine deaminase inhibitors. J. Med. Chem., 2011, 54(1), 107-121.
[4]
Cristalli, G.; Eleuteri, A.; Volpini, R.; Vittori, S.; Camaioni, E.; Lupidi, G. Adenosine deaminase inhibitors: Synthesis and structure-activity relationships of 2-hydroxy-3-nonyl derivatives of azoles. J. Med. Chem., 1994, 37(1), 201-205.
[5]
Mardanyan, S.; Sharoyan, S.; Antonyan, A.; Armenyan, A.; Cristalli, G.; Lupidi, G. Tryptophan environment in adenosine deaminase. I. Enzyme modification with N-bromosuccinimide in the presence of adenosine and EHNA analogues. Biochim. Biophys. Acta, 2001, 1546, 185-195.
[6]
Agarwal, R.P. Inhibitors adenosine deaminase. Pharmacol. Ther., 1982, 17(3), 399-429.
[7]
Glazer, R.I. Adenosine deaminase inhibitors: Their role in chemotherapy and immunosuppression. Cancer Chemother. Pharmacol., 1980, 4(4), 227-235.
[8]
Iaroshenko, V.O.; Ostrovskyi, D.; Petrosyan, A.; Mkrtchyan, S.; Villinger, A.; Langer, P. Synthesis of fluorinated purine and 1-deazapurine glycosides as potential inhibitors of adenosine deaminase. J. Org. Chem., 2011, 76(8), 2899-2903.
[9]
Jeanettethomas, H.; Riordan, J.; Montgomery, J. The synthesis of coformycin from 5-amino-1-î2-d-ribofuranosylimidazole-4-carboxamide. Nucleosides Nucleotides, 1986, 5(4), 431-439.
[10]
Spiers, A.S.; Moore, D.; Cassileth, P.A.; Harrington, D.P.; Cummings, F.J.; Neiman, R.S.; Bennett, J.M.; O’Connell, M.J. Remissions in hairy-cell leukemia with pentostatin (2′-deoxycoformycin). N. Engl. J. Med., 1987, 316(14), 825-830.
[11]
Lee, G.; Lee, S.S.; Kay, K.Y.; Kim, D.W.; Choi, S.; Jun, H.K. Isolation and characterization of a novel adenosine deaminase inhibitor, IADA-7, from Bacillus sp. J-89. J. Enzyme Inhib. Med. Chem., 2009, 24(1), 59-64.
[12]
Xu, X. New concepts and approaches for drug discovery based on traditional Chinese medicine. Drug Discov. Today. Technol., 2007, 3(3), 247-253.
[13]
Sucher, N.J. The application of Chinese medicine to novel drug discovery. Expert Opin. Drug Discov., 2013, 8(1), 21-34.
[14]
Cragg, G.M.; Newman, D.J. Natural products: a continuing source of novel drug leads. Biochim.et Biophys. Acta, 2013, 1830(6), 3670-3695.
[15]
Farnsworth, N.R.; Akerele, O.; Bingel, A.S. Medicinal plants in therapy. Bull. World Health Organ., 1984, 19(3), 336-336.
[16]
Xu, X.; Zhu, L.; Chen, L. Separation and screening of compounds of biological origin using molecularly imprinted polymers. J. Chromatogr. B ., 2004, 804(1), 61-69.
[17]
Pfrogner, N. Adenosine deaminase from calf spleen. II. Chemical and enzymological properties. Arch. Biochem. Biophys., 1967, 119(1), 147-154.
[18]
Tritsch, G.L. Validity of the continuous spectrophotometric assay of Kalckar for adenosine deaminase activity. Anal. Biochem., 1983, 129(1), 207-209.
[19]
Dong, P.; Zhang, X.; Liu, Y.; Tang, P.; Yuan, S.U.; Minshan, S.U.; Han, X.; Shao, N. Rapid drug model for screening adenosine deaminase inhibitor. Chinese J. Modern Appl. Pharm., 2015, 32(11), 1301-1305.
[20]
Chen, S.; Hsieh, J.H.; Huang, R.; Sakamuru, S.; Hsin, L.Y.; Xia, M.; Shockley, K.R.; Auerbach, S.; Kanaya, N.; Lu, H. Cell-based high-throughput screening for aromatase inhibitors in the Tox21 10K library. Toxicol. Sci., 2015, 147(2), 446-457.
[21]
Zhang, X.G.; Liu, Z.Y.; Liu, J.W.; Zeng, Y.L.; Guo, G.J.; Sun, Q.Y. Antitumor activity of a Rhodococcus sp. Lut0910 isolated from polluted soil. Tumour Biol., 2017, 39(6)1010428317711661
[22]
Zhang, F.; Zeng, Y.L.; Zhang, X.G.; Chen, W.J.; Yang, R.; Li, S.J. RNA interference targeting extracellular matrix metalloproteinase inducer (CD147) inhibits growth and increases chemosensitivity in human cervical cancer cells. Eur. J. Gynaecol. Oncol., 2013, 34(5), 429-435.
[23]
Chen, Y.; Yuan, Q.; Shan, L.; Lin, M.; Cheng, D.; Changyu, L.I. Antitumor activity of bacterial exopolysaccharides from the endophyte Bacillus amyloliquefaciens sp. isolated from Ophiopogon japonicus. Oncol. Lett., 2013, 5(6), 1787-1792.
[24]
Zhang, Q.; Song, C.; Zhao, J.; Shi, X.; Sun, M.; Liu, J.; Fu, Y.; Jin, W.; Zhu, B. Separation and characterization of antioxidative and angiotensin converting enzyme inhibitory peptide from jellyfish gonad hydrolysate. Molecules, 2018, 23(1), 94.
[25]
Wang, S-D.; Ma, Q.; Wang, K.; Ma, P-B. Strong and biocompatible three-dimensional porous silk fibroin/graphene oxide scaffold prepared by phase separation. Int. J. Biol. Macromol., 2018, 111, 237-246.
[26]
Li, J.; Zhang, J.; Lai, B.; Zhao, Y.; Li, Q. Cloning, expression, and characterization of capra hircus golgi α-mannosidase II. Appl. Biochem. Biotechnol., 2015, 177(6), 1241-1251.
[27]
Wang, G.; Qiu, J.; Xiao, X.; Cao, A.; Zhou, F. Synthesis, biological evaluation and molecular docking studies of a new series of chalcones containing naphthalene moiety as anticancer agents. Bioorg. Chem., 2018, 76, 249-257.
[28]
Cohen, P.A.; Towers, G.H.N. Anthraquinones and phenanthroperylenequinones from Nephroma laevigatum. J. Nat. Prod., 1995, 58(4), 520-526.
[29]
Xin, C.; Sun, A.; Liu, R. Preparative isolation and purification of five compounds from the Chinese medicinal herb Polygonum cuspidatum Sieb. et Zucc by high-speed counter-current chromatography. J. Chromatogr. A, 2005, 1097(1), 33-39.
[30]
Villatoro, B.S.D.; Gónzalez, F.G.; Polonsky, J.; Baskevitch-Varon, Z. Chrysophanic acid, chrysophanein and chaparrin from. Phytochemistry, 1974, 13(9), 2018-2019.
[31]
Hagiwara, H.; Nakamura, T.; Okunaka, N.; Hoshi, T.; Suzuki, T. Catalytic performance of ruthenium-supported ionic-liquid catalysts in sustainable synthesis of macrocyclic lactones. Helv. Chim. Acta, 2010, 93(1), 175-182.
[32]
Piao, H.S.; Jin, G.Z. Study on chemical constituents of petroleum ether fraction from caragana microphylla lam. Li Shizhen Med. Materia Medica Res., 2007, 18(1), 111-112.
[33]
Jin, X.M. Studies on natural anthraquinone antitumor active ingredients and preparation of derivatives., PhD Thesis, June. 2007.
[34]
Zhang, X.; Geoffroy, P.; Miesch, M.; Julien-David, D.; Raul, F.; Aoudé-Werner, D.; Marchioni, E. Gram-scale chromatographic purification of β-sitosterol: Synthesis and characterization of β-sitosterol oxides. Steroids, 2005, 70(13), 886-895.
[35]
Seebacher, W.; Simic, N.; Weis, R.; Saf, R.; Kunert, O. Complete assignments of 1 H and 13 C NMR resonances of oleanolic acid, 18α-oleanolic acid, ursolic acid and their 11-oxo derivatives. MRC, 2010, 41(8), 636-638.
[36]
Jones, K.; Hughes, J.; Hong, M.; Jia, Q.; Orndorff, S. Modulation of melanogenesis by aloesin: A competitive inhibitor of tyrosinase. Pigment Cell Res., 2010, 15(5), 335-340.
[37]
Plumb, J.A. Cell sensitivity assays: The MTT assay. Methods Mol. Biol., 2011, 731(88), 237-245.
[38]
Twentyman, P.R.; Luscombe, M. A study of some variables in a tetrazolium dye (MTT) based assay for cell growth and chemosensitivity. Br. J. Cancer, 1987, 56(3), 279-285.
[39]
Ni, H.; Li, Y-H.; Hao, R-L.; Li, H.; Hu, S-Q.; Li, H-H. Identification of adenosine deaminase inhibitors from Tofu wastewater and litchi peel and their synergistic anticancer and antibacterial activities with cordycepin. Int. J. Food Sci. Technol., 2016, 51(5), 1168-1176.
[40]
Chen, W.; Zheng, R.; Baade, P.D.; Zhang, S.; Zeng, H.; Bray, F.; Jemal, A.; Yu, X.Q.; He, J. Cancer statistics in China, 2015. CA Cancer J. Clin., 2016, 66(2), 115-132.
[41]
Hidaka, T.; Katayama, K.; Yamashita, K.; Yamashita, T.; Watanabe, K.; Shimazaki, M.; Ohno, M.; Takeuchi, T.; Umezawa, H. Effects of a new adenosine deaminase inhibitor, isocoformycin, on toxicity, antitumor activity and tissue distribution of formycin A and 9-beta-D-arabinofuranosyladenine. J. Antibiot. , 1980, 33(3), 303-309.
[42]
Wu, J.Z.; Walker, H.; Lau, J.Y.; Hong, Z. Activation and deactivation of a broad-spectrum antiviral drug by a single enzyme: adenosine deaminase catalyzes two consecutive deamination reactions. Antimicrob. Agents Chemother., 2003, 47(1), 426-431.
[43]
Tuli, H.S.; Sharma, A.K.; Sandhu, S.S.; Kashyap, D. Cordycepin: A bioactive metabolite with therapeutic potential. Life Sci., 2013, 93(23), 863-869.
[44]
Tortorella, C.; Rovaris, M.; Filippi, M. Cladribine. Ortho Biotech Inc. Curr. Opin. Investig. Drugs, 2001, 2(12), 1751-1756.
[45]
King, K.M.; Damaraju, V.L.; Vickers, M.F.; Yao, S.Y.; Thach, L.; Tackaberry, T.E.; Mowles, D.A.; Ng, A.M.L.; Young, J.D.; Cass, C.E. A comparison of the transportability, and its role in cytotoxicity, of clofarabine, cladribine, and fludarabine by recombinant human nucleoside transporters produced in three model expression systems. Mol. Pharmacol., 2006, 69(1), 346-353.
[46]
Guchelaar, H.J.; Richel, D.J.; Schaafsma, M.R. Clinical and toxicological aspects of the antineoplastic drug cladribine: A review. Ann. Hematol., 1994, 69(5), 223-230.
[47]
Mitchell, B.S.; Koller, C.A.; Heyn, R. Inhibition of adenosine deaminase activity results in cytotoxicity to T lymphoblasts in vivo. Blood, 1980, 56(3), 556-559.
[48]
Chen, Y.; Zhu, J.; Zhang, W. Antitumor effect of traditional Chinese herbal medicines against lung cancer. Anticancer Drugs, 2014, 25(9), 983-991.
[49]
Jiao, L.; Bi, L.; Lu, Y.; Wang, Q.; Gong, Y.; Shi, J.; Xu, L. Cancer chemoprevention and therapy using chinese herbal medicine. Biol. Proced. Online, 2018, 20(1), 1.
[50]
Srinivas, G.; Anto, R.P.; Vidhyalakshmi, S.; Senan, V.P.; Karunagaran, D. Emodin induces apoptosis of human cervical cancer cells through poly(ADP-ribose) polymerase cleavage and activation of caspase-9. Eur. J. Pharmacol., 2003, 473(2), 117-125.
[51]
Lee, H.Z.; Hsu, S.L.; Liu, M.C.; Wu, C.H. Effects and mechanisms of aloe-emodin on cell death in human lung squamous cell carcinoma. Eur. J. Pharmacol., 2001, 431(3), 287-295.
[52]
Shieh, D.E.; Chen, Y.Y.; Yen, M.H.; Chiang, L.C.; Lin, C.C. Emodin-induced apoptosis through p53-dependent pathway in human hepatoma cells. Life Sci., 2004, 74(18), 2279-2290.
[53]
Kaul, A.; Sethi, R.; Misra, M.K. Evaluation of the roles of adenosine deaminase and xanthine oxidase in reperfusion injury in patients with myocardial infarction. Clin. Chim. Acta, 2007, 380(1), 225-227.
[54]
Nakamura, K.; Yoshikawa, N.Y.; Kagota, S.; Shinozuka, K.; Kunitomo, M. Antitumor effect of cordycepin (3′-deoxyadenosine) on mouse melanoma and lung carcinoma cells involves adenosine A3 receptor stimulation. Anticancer Res., 2006, 26(1A), 43-47.
[55]
Kodama, E.N.; Mccaffrey, R.P.; Yusa, K.; Mitsuya, H. Antileukemic activity and mechanism of action of cordycepin against terminal deoxynucleotidyl transferase-positive (TdT+) leukemic cells. Biochem. Pharmacol., 2000, 59(3), 273-281.
[56]
Johns, D.G.; Adamson, R.H. Enhancement of the biological activity of cordycepin (3′-deoxyadenosine) by the adenosine deaminase inhibitor 2′-deoxycoformycin. Biochem. Pharmacol., 1976, 25(12), 1441-1444.
[57]
Yung-Jen, T.; Lie-Chwen, L.; Tung-Hu, T. Pharmacokinetics of adenosine and cordycepin, a bioactive constituent of Cordyceps sinensis in rat. J. Agric. Food Chem., 2010, 58(8), 4638-4643.
[58]
Williamson, J.; Scott-Finnigan, T.J. Trypanocidal activity of antitumor antibiotics and other metabolic inhibitors. Antimicrob. Agents Chemother., 1978, 13(5), 735-744.

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