P. Zhu et al. / Bioorg. Med. Chem. Lett. 19 (2009) 6966–6969
6969
8. (a) Fukushima, M.; Matsuyama, F.; Ueda, N.; Egawa, K.; Takemoto, J.; Kajimoto,
Y.; Yonaha, N.; Miura, T.; Kaneko, T.; Nishi, Y.; Mitsui, R.; Fujita, Y.; Yamada, Y.;
Seino, Y. Diabetes Res. Clin. Pract. 2006, 73, 174; (b) Wen, X. A.; Sun, H. B.; Liu, J.;
Wu, G. Z.; Zhang, L. Y.; Wu, X. M.; Ni, P. Z. Bioorg. Med. Chem. Lett. 2005, 15,
4944; (c) Chen, J.; Liu, J.; Zhang, L. Y.; Wu, G. Z.; Hua, W. Y.; Wu, X. M.; Sun, H. B.
Bioorg. Med. Chem. Lett. 2006, 16, 2915.
in the future, become potential drug candidates for treating dis-
eases caused by abnormalities in glycogen metabolism.14 Further
research on GPa inhibition in vivo and SAR studies of 23-hydroxy-
betulinic acid are ongoing in our laboratory and the results will be
reported in due course.
9. Ye, W. C.; Ji, N. N.; Zhao, S. X.; Liu, J. H.; Ye, T.; Mckervey, M. A.; Stevensin, P.
Phytochemistry 1996, 42, 799.
Acknowledgments
10. (a) Ji, Z. N.; Ye, W. C.; Liu, G. G.; Wendy Hsiao, W. L. Life Sci. 2002, 72, 1; (b) Bi,
Y.; Xu, J. Y.; Wu, X. M.; Ye, W. C.; Yuan, S. T.; Zhang, L. Y. Bioorg. Med. Chem. Lett.
2007, 17, 1475.
This work was supported by National Natural Science Fund
Committee for the investigation support (No. 30472083) and Jiang-
su Natural Science Foundation (Grant BK2005101) and Xiansheng
Ph.D. Program Foundation (No. 02704003).
11. Pisha, E.; Chai, H.; Lee, I. S.; Chagwedera, T. E.; Farnsworth, N. R.; Cordell, G. A.;
Beecher, C. W. W.; Fong, H. H. S.; Kinghorn, A. D.; Brown, D. M.; Wani, M. C.;
Wall, M. E.; Hieken, T. J.; Dasgupta, T. K.; Pezzuto, J. M. Nat. Med. 1995, 1,
1046.
12. Analytical data for compound 12b: mp 80–82 °C; IR (KBr, cmÀ1):
m 3472, 2936,
2859, 1731, 1633, 1535, 1448, 1369, 1247, 1045, 882; 1H NMR (CDCl3,
300 MHz): d 0.80, 0.87, 0.93, 0.96, 1.68 (s, 3H each, 24, 25, 26, 27, 30-CH3), 2.01,
2.06 (s, 3H each, 3 and 23-OCOCH3), 2.17 (m, 2H, 28-CONH(CH2)6NH2), 2.47 (m,
1H, 19-CH), 3.17 (m, 4H, 28-CONHCH2(CH2)4CH2NH2), 3.68, 3.84 (dd, 1H each,
JA = JB = 11.52 Hz, 23-CH2), 4.59, 4.73 (d, 1H each, 29=CH2), 4.76 (m, 1H, 3-CH),
5.65 (m, 1H, 28-CONH(CH2)6NH2); 13C NMR (DMSO-d6, 125 MHz): d 12.7, 14.3,
15.9, 16.3, 17.6, 19.2, 20.7, 20.8, 21.0, 22.9, 25.3, 26.3, 26.5, 28.9, 29.4, 30.5,
32.6, 33.3, 33.7, 36.6, 36.8, 37.7, 37.8, 38.3, 40.0, 40.4, 41.6, 42.0, 46.3, 47.9,
49.8, 50.2, 55.0, 64.9 (23-C), 73.9 (3-C), 109.3 (29-C), 151.1 (20-C),
170.0(CH3CO), 170.2(CH3CO), 175.4 (28-C). EIMS: [M+H]+ 655.5.
References and notes
1. Kurukulasuriya, R.; Link, J. T.; Madar, D. J.; Pei, Z.; Richards, S. J.; Rohde, J. J.;
Souers, A. J.; Szczepankiewicz, B. G. Curr. Med. Chem. 2003, 10, 123.
2. Aiston, S.; Coghlan, M. P.; Agius, L. Eur. J. Biochem. 2003, 270, 2773.
3. (a) Lu, Z. J.; Bohn, J.; Bergeron, R.; Deng, Q. L.; Ellsworth, K. P.; Geissler, W. M.;
Harris, G.; McCann, P. E.; Mckeever, B.; Myers, R. W.; Saperstein, R.;
Willoughby, C. A.; Yao, J.; Chapman, K. Bioorg. Med. Chem. Lett. 2003, 13,
4125; (b) Wright, S. W.; Rath, V. L.; Genereux, P. E.; Hageman, D. L.; Levy, C. B.;
McClure, L. D.; McCoid, S. C.; McPherson, R. K.; Schelhorn, T. M.; Wilder, D. E.;
Zavadoski, W. J.; Gibbs, E. M.; Treadway, J. L. Bioorg. Med. Chem. Lett. 2005, 15,
459; (c) Treadway, J. L.; Mendys, P.; Hoover, D. J. Exp. Opin. Invest. Drugs 2001,
10, 439. and references cited therein.
13. The biological assay procedure for target compounds: Each compound was
dissolved in DMSO and diluted at different concentrations for IC50
determination. The enzymes were added into the 100 ll buffer with
compounds dissolved in containing 50 mM Hepes (pH 7.2), 100 mM KCl,
2.5 mM MgCl2, 0.5 mM glucose-1-phosphate, and 1 mg/ml glycogen in 96-well
microplates. After the addition of 150 ll of 1 M HCl containing 10 mg/ml
5. Bollen, M.; Keppens, S.; Stalmans, W. Biochem. J. 1998, 336, 19.
6. (a) Pinotsis, N.; Leonidas, D. D.; Chrysina, E. D.; Oikonomakos, N. G.; Mavridis, I.
M. Protein Sci. 2003, 12, 1914; (b) Chrysina, E. D.; Kosmopolou, M. N.; Tiraidis,
C.; Kardarakis, R.; Bischler, N.; Leonidas, D. D.; Hadady, Z.; Somsak, L.; Docsa, T.;
Gergely, P.; Oikonomakos, N. G. Protein Sci. 2005, 14, 873.
ammonium molybdate and 0.38 mg/ml malachite green, reactions were run at
22 °C for 25 min. And then the phosphate absorbance was measured at
655 nm. The IC50 values were estimated by fitting the inhibition data to a dose-
dependent curve using a logistic derivative equation.
14. Wu, X. M.; Xu, J. Y.; Bi, Y.; Ye, W. C.; Yuan, S. T.; Zhang, L. Y. Chinese Patent: ZL
200610040277.2, 2009.
7. Dzubak, P.; Hajduch, M.; Vydra, D.; Hustova, A.; Kvasnica, M.; Biedermann, D.;
Markova, L.; Urban, M.; Sarek, J. Nat. Prod. Rep. 2006, 23, 394.