Y. Wu et al. / Bioorg. Med. Chem. Lett. 19 (2009) 1818–1821
1821
Table 1
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Life Sci. 2004, 74, 2379.
Cytotoxic activities of isosteviol derivatives against B16-F10 melanoma cells
10. Braguinu, W. L.; Gomes, M. A. B.; Oliveira, B. H.; Garnieri, E. G. S.; Rocha, M. E.
M.; Oliveira, M. B. M. Toxicol. Lett. 2003, 143, 83.
Compound
B16-F10
Compound
B16-F10
Compound
B16-F10
11. Wu, Y. C.; Hung, F. R.; Cosentino, M.; Wang, H. K.; Lee, K. H. J. Nat. Prod. 1996,
59, 635.
12. Xu, D. Y.; Zhang, S. J.; David, J. R.; Wang, J. P. Clin. Exp. Pharmacol. Physiol. 2007,
34, 488.
13. Kataev, V. E.; Militsina, O. I.; Strobykina, I. Yu.; Kovylyaeva, G. I.; Musin, R. Z.;
Fedorova, O. V.; Rusinov, G. L.; Zueva, M. N.; Mordovskoi, G. G.; Tolstikov, A. G.
Pharm. Chem. J. 2006, 40, 473.
14. Wong, K. L.; Lin, J. W.; Liu, J. C.; Yang, H. Y.; Kao, P. F.; Chen, C. H.; Loh, S. H.;
Chiu, W. T.; Cheng, T. H.; Lin, J. G.; Hong, H. J. Pharmacology 2006, 76, 163.
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16. Amr, A. E.; Hegab, M. I.; Ibrahim, A. A.; Abdalah, M. M. Monatch. Chem. 2003,
134, 1395.
1
2
3
4
5
6
7
NIa
NIa
NIa
58b
NIa
NIa
68b
8
9
NIa
25b
22b
NIa
NIa
26b
24b
19
20
22
23
26
27
29
34.3c
27.5b
15b
10
12
13
15
16
NIa
19b
21b
NIa
a
No inhibition at 100 lV.
b
c
IC50
(lM).
Inhibition (%) determined at 100
l
M concentration of compound.
17. Amr, A. E.; Abou-Ghalia, M. H. Amino Acids 2004, 26, 283.
18. Brana, M. F.; Castellano, J. M.; Mpran, M.; Perez de Vega, M. J.; Gian, X. D.;
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protons of hydroxyl group and amine group were necessary in po-
tency (4 vs 5, 7 vs 8 and 22 vs 23). The isoxazolidine derivative 22
(IC50 = 15
tive 27 (IC50 = 21
B16-F10 melanoma cells, indicating that D-ring fused heterocyclic
analogues might deserve some attention for further cytotoxic
activities design.
In summary, a novel series of 15- and 16-substituted isosteviol
derivatives were first prepared, especially some new compounds
containing pyrazoline and isoxazolidine ring fused with isosteviol
structure were stereoselectively synthesized from compound 7
via Grob fragmentation and subsequent intramolecular 1,3-dipolar
cycloaddition. The cytotoxic activities in vitro of these new isostev-
iol derivatives were investigated, and some of them showed note-
worthy activities against B16-F10 melanoma cells. Further
research and drug development on isosteviol derivatives for cyto-
toxicity test are ongoing in our laboratory and the results will be
reported in due course.
l
M), pyrazole 26 (IC50 = 19
l
M) and pyrazoline deriva-
20. Amr, A. E. G. E.; Abdel-Latif, N. A.; Abdalla, M. M. Bioorg. Med. Chem. 2006, 14,
373.
21. Ahn, J. H.; Kim, H. M.; Jung, S. H.; Kang, S. K.; Kim, K. R.; Rhee, S. D.; Yang, S. D.;
Cheon, H. G.; Kim, S. S. Bioorg. Med. Chem. Lett. 2004, 14, 4461.
22. Cui, P.; Macdonald, T. L.; Chen, M.; Nadler, J. L. Bioorg. Med. Chem. Lett. 2006, 16,
3401.
23. Renslo, A. R.; Luehr, G. W.; Lam, S.; Westlund, N. E.; Gómez, M.; Hackbarth, C. J.;
Patel, D. V.; Gordeev, M. F. Bioorg. Med. Chem. Lett. 2006, 16, 3475.
24. Aiello, E.; Aiello, S.; Mingoia, F.; Bacchi, A.; Pelizzi, C.; Musiu, C.; Giovanna, S.
M.; Pani, A.; La, C. P.; Elena, M. M. Bioorg. Med. Chem. 2000, 8, 2719.
25. Liu, H. M.; Liu, F. W.; Zou, D. P.; Dai, G. F. Bioorg. Med. Chem. Lett. 2005, 15, 1821.
26. Liu, X. F.; Huang, X.; Xu, H. S. Wuhan Daxue Xuebao (Ziran Kexueban) 1994, 2, 74.
27. Al’fonsov, V. A.; Bakaleinik, G. A.; Gubaidullin, A. T.; Kataev, V. E.; Kovylyaeva,
G. I. Russ. J. Gen. Chem. 2000, 70, 953.
28. Crystallographic data (excluding structure factors) has been deposited with the
Cambridge Crystallographic Data Centre as supplementary publication
numbers CCDC 654209 (compound 4), 257291 (compound 6) and 701082
(compound 12). Copies of the data can be obtained, free of charge, on
applications to CCDC, 12 Union Road, Cambridge CB2 1EZ. UK (fax: +44 (0)
lM) exhibited more inhibitory potency against
1223
336033
or
E-mail:
or
29. Tao, J. C.; Tian, G. Q.; Zhang, Y. B.; Fu, Y. Q.; Dai, G. F.; Wu, Y. Chin. Chem. Lett.
2005, 16, 1441.
30. Schneider, G.; Bottka, S.; Hackler, L.; Wölfling, J.; Sohár, P. Liebigs Ann. Chem.
1989, 263.
Acknowledgment
The authors are grateful for the financial support to the National
Natural Science Foundation of China (Project No. 20772113).
31. Snider, B. B.; Lin, H.; Foxman, B. M. J. Org. Chem. 1998, 63, 6442.
32. Frank, E.; Wolfling, J.; Aukszi, B.; Konig, V.; Schneider, T. R.; Schneider, G.
Tetrahedron 2002, 58, 6843.
33. Roy, A.; Sahabuddin, S. K.; Achari, B.; Mandal, S. B. Tetrahedron 2005, 61, 365.
34. Emmanuvel, L.; Shaikh, T. M. A.; Sudalai, A. Org. Lett. 2005, 7, 5071.
35. In vitro cytotoxicity study: B16-F10 melanoma cells (purchased from Nanjing
KeyGen Biotech. Co. Ltd, China), was cultured in RPMI-1640 medium (GIBCO
Co. Grand Island, NY) supplemented with 10% FBS, 100 IU/mL penicillin, and
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