Synthesis and biological evaluation of furoxan-based nitric oxide-releasing derivatives of glycyrrhetinic acid as anti-hepatocellular carcinoma agents

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 22, 2010, Pages 6416-6420

  Lai, Yisheng ^a   Shen, Lihong ^a,b   Zhang, Zhenzhen ^a   Liu, Wenqing ^a   Zhang, Yihua ^a   Ji, Hui ^a   Tian, Jide ^c  

^a CHINA PHARMACEUTICAL UNIVERSITY   (China)

^b HANDAN COLLEGE   (China)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Anti hepatocellular carcinoma agent; Furoxan; Glycyrrhetinic acid; Hybrid compound; NO donor; NO releasing

Indexed keywords

ANTINEOPLASTIC AGENT; GLYCYRRHETINIC ACID DERIVATIVE; HEMOGLOBIN; NITRIC OXIDE DONOR;

ARTICLE; CARCINOMA CELL; CELL GROWTH; CELL STRAIN HEPG2; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; CYTOTOXICITY TEST; DRUG ACTIVITY; DRUG DESIGN; DRUG POTENTIATION; DRUG STRUCTURE; DRUG SYNTHESIS; EVALUATION; HUMAN; HUMAN CELL; IC 50; LIVER CELL; LIVER CELL CARCINOMA; STRUCTURE ACTIVITY RELATION;

ANTINEOPLASTIC AGENTS; CARCINOMA, HEPATOCELLULAR; CELL LINE, TUMOR; GLYCYRRHETINIC ACID; HUMANS; LIVER NEOPLASMS; NITRIC OXIDE; OXADIAZOLES;

EID: 77958067172     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.09.070     Document Type: Article

References (33)

1. S. Mocellin Curr. Cancer Drug Targets 9 2009 214
2. J.A. Coulter, H.O. McCarthy, J. Xiang, W. Roedl, E. Wagner, T. Robson, and D.G. Hirst Nitric Oxide 19 2008 192
3. D.A. Wink, L.A. Ridnour, S.P. Hussain, and C.C. Harris Nitric Oxide 19 2008 65
4. D. Hirst, and T. Robson Curr. Pharm. Des. 16 2010 411
5. H. Yasuda, M. Yamaya, K. Nakayama, T. Sasaki, H. Ebihara, A. Kanda, M. Asada, D. Inoue, T. Suzuki, T. Okazaki, H. Takahashi, M. Yoshida, T. Kaneta, K. Ishizama, S. Yamanda, N. Tomita, M. Yamasaki, A. Kikuchi, H. Kubo, and H. Sasaki J. Clin. Oncol. 24 2006 688
6. D.R. Seimens, J. Heaton, M. Adams, and C. Graham Nitric Oxide 17 2007 S15
7. D.R. Siemens, J.P. Heaton, M.A. Adams, J. Kawakami, and C.H. Graham Urology 74 2009 878
8. H. Cerecetto, and W. Porcal Mini-Rev. Med. Chem. 5 2005 57
9. S. Moharram, A. Zhou, L.I. Wiebe, and E.E. Knaus J. Med. Chem. 47 2004 1840
10. D. Maksimovic-Ivanic, S. Mijatovic, L. Harhaji, D. Miljkovic, D. Dabideen, K. Fan Cheng, K. Mangano, G. Malaponte, Y. Al-Abed, M. Libra, G. Garotta, F. Nicoletti, and S. Stosic-Grujicic Mol. Cancer Ther. 7 2008 510
11. M. Boiani, H. Cerecetto, M. González, M. Risso, C. Olea-Azar, O.E. Piro, E.E. Castellano, A. López de Ceráin, O. Ezpeleta, and A. Monge-Vega Eur. J. Med. Chem. 36 2001 771
12. M.N. Asl, and H. Hosseinzadeh Phytother. Res. 22 2008 709
13. H. Hibasami, H. Iwase, K. Yoshioka, and H. Takahashi Int. J. Mol. Med. 17 2006 215
14. M. Kimura, H. Inoue, K. Hirabayashi, H. Natsume, and M. Ogihara Eur. J. Pharmacol. 431 2001 151
15. D. Armanini, I. Karbowiak, and J.W. Funder Clin. Endocrinol. 19 1983 609
16. M. Nose, M. Ito, K. Kamimura, M. Shimizu, and Y. Ogihara Planta Med. 60 1994 136
17. G. Lin, I.P. Nnane, and T.V. Cheng Toxicon 37 1999 1259
18. E. Gumpricht, R. Dahl, M.W. Devereaux, and R.J. Sokol J. Biol. Chem. 280 2005 10556
19. R.W. Li, Y.H. Zhang, H. Ji, X.L. Yu, and S.X. Peng Acta Pharm. Sin. 36 2001 821
20. X. Su, H. Lawrence, D. Ganeshapillai, A. Cruttenden, A. Purohit, M.J. Reed, N. Vicker, and B.V. Potter Bioorg. Med. Chem. 12 2004 4439
21. P.D. Dean, T.G. Halsall, and M.W. Whitehouse J. Pharm. Pharmacol. 19 1967 682
22. General procedure for the synthesis of the target compounds 4a-h: DMAP (0.1 mmol) and appropriate phenylsulfonylfuroxans 1a-h (0.31 mmol) were added to a mixture solution of 3-O-hemisuccinate GA methyl ester 3 (0.26 mmol) and DCC (0.33 mmol) in dry dichloromethane. The reaction mixture was stirred at room temperature for 24 h. Filtration and removal of the solvent in vacuo afforded the crude product, which was subsequently purified by column chromatography using (PE/EtOAc = 3:1) to give pure 4a-h in 65-70% yields.
23. X. Song, P.L. Lorenzi, C.P. Landowski, B.S. Vig, J.M. Hilfinger, and G.L. Amidon Mol. Pharm. 2 2005 157
24. M. Deshmukh, P. Chao, H.L. Kutscher, D. Gao, and P.J. Sinko J. Med. Chem. 53 2010 1038
25. Y. Ling, X. Ye, H. Ji, Y. Zhang, Y. Lai, S. Peng, and J. Tian Bioorg. Med. Chem. 18 2010 3448
26. 4, and concentrated under reduced pressure. The crude product was purified by column chromatography (PE/EtOAc = 2:1) to yield 7a-g.
27. 10S: C, 64.45; H, 7.01; N, 5.12. Found: C, 64.25; H, 7.06; N, 5.03.
28. K. Sakano, and M. Ohshima Agric. Biol. Chem. 50 1986 763
29. General procedure for the synthesis of the target compounds 13a, 13b, 13d, 13e and 13g: 3-Acetoxy-glycyrrhetinic acid 9 (6.0 mmol) dissolved in dry dichloromethane (20 mL), was added oxalyl chloride (3.0 mL) by slow dropwise. The mixture was stirred at room temperature for 4 h, followed by concentration under reduced pressure to 3-acetoxy-11-oxo-olean-12-en-30-oyl chloride 12. A mixture of 12 (0.52 mmol) and appropriate phenylsulfonylfuroxans 1a-g (0.53 mmol) in dry THF (20 mL) was refluxed in presence of triethylamine (0.2 mL) for 12 h. The solution was cooled to room temperature. After filtration, the filtrate was evaporated in vacuo and the crude product was purified by column chromatography (PE/EtOAc = 5:1) to obtain pure 13a, 13b, 13d, 13e and 13g in 80-85% yield.
30. 5/well were cultured in 96-well plates overnight and treated in triplicate with different concentrations of individual compounds for 24 h. Cells cultured in medium alone or treated with vehicle were used as negative controls. During the last 4 h incubation, the cells were exposed to MTT (5 mg/mL, sigma) and the resulting formazan crystals were dissolved in 200 μM DMSO, followed by measuring at 570 nm on a microplate reader (Thermo, USA).
31. S. Chintharlapalli, S. Papineni, I. Jutooru, A. McAlees, and S. Safe Mol. Cancer Ther. 6 2007 1588
32. Nitrate/nitrite measurement in vitro: The human hepatocellular carcinoma (HepG2, BEL-7402) and non-tumor liver (LO2) cells were cultured in the 24-well plates for 24 h and treated in triplicate with 100 μM of individual compounds for 30-300 min. The cells were harvested longitudinally and their lysates were prepared. The levels of nitrate/nitrite in the lysates were determined using the nitrate/nitrite colorimetric assay kit, according to manufacturers' instruction (Beyotime, China).
33. C.S. Lee, Y.J. Kim, M.S. Lee, E.S. Han, and S. Lee Life Sci. 83 2008 481