Abstract
Two series of novel spin-labeled derivatives of Cinobufagin(compounds 5 and 8a―8f in series 1 with five-membered ring nitroxyl free radical and compounds 6 and 9a―9f in series 2 with six-membered ring nitroxyl free radical) were synthesized. The cytotoxic activities in vitro against two tumor cell lines(HepG2 and HeLa) were evaluated, and the results indicate that all compounds display potent cytotoxicity against HepG2 and HeLa cells, and most compounds show better activities on HeLa cells than on HepG2 cells except for compounds 8a and 9d. Generally, the compounds in series 2 have more potent cytotoxic activity against HepG2 than the compounds in series 1. Especially, compounds 6 and 9f in series 2 exhibit even more potent activities against the two tumor cell lines than Cinobufagin. Thus incorporation of different L-amino acids as the linker changed the cytotoxic profile of the spin-labeled Cinobufagin. In addition, the representative compound 9f significantly changed the cell cycle distribution and led to HeLa cell cycle arrested at G2/M phase.
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References
World Health Organization, World Cancer Day―"Together It Is Possible", [EB/OL], http://www.who.int/cancer/en/[2012-3-30]
Tan Y. F., Sun X. H., Dong F. Y., Tian H. Y., Jiang R. W., Chin. J. Chem., 2015, 33, 1084
Chen Q., Lin J. H., Zhao D., Zhu X., Chem. Res. Chinese Universi-ties, 2016, 32(4), 792
Hong Z., Chan K., Yeung H. W., J. Pharm. Pharmacol., 1992, 44, 1023
Wang J., Jin W., Jin H., Zhou F., China Journal of Chinese Materia Medica, 1998, 23, 651
Yeh J. Y., Huang W. J., Kan S. F., Wang P. S., The Prostate, 2003, 54, 112
Wang L., Wu J., Li M., Yang X. W., Cui J. R., Chin. J. Oncol., 2006, 27, 717
Wang X. L., Zhao G. H., Zhang J., Shi Q. Y., Guo W. X., Tian X. L., Qiu J. Z., Yin L. Z., Deng X. M., Song Y., J. Asian Nat. Prod. Res., 2011, 13, 383
Ye M., Ning L. L., Zhan J. X., Guo H. Z., Guo D. A., Journal of Mo-lecular Catalysis B, Enzymatic, 2003, 22, 89
Zhou M. Q., Hou Y. P., Hamza A., Zhan C. G., Bugni T. S., Thorson J. S., Org. Lett., 2012, 14, 5424
Jin Y., Chen S. W., Tian X., Biorg. Med. Chem., 2006, 14, 3062
Gadjeva V. G., Int. J. Pharm., 2002, 247, 39
Jing X. H., Zhang J. Q., Zhang Z. W., Tian X., Chem. Res. Chinese Universities, 2010, 26(5), 753
Yang L., Liu Y. Q., Tan H., Li W. G., Tian X., Nat. Prod. Res., 2007, 21, 998
Liu Y., Wang M. J., Zhang Z. J., Morris-Natschke S. L., Goto M., Jing T., Liu Y. Q., Wang C. Y., Xuan T., Yang X. M., Med. Chem. Res., 2014, 23, 3269
Liu Y. Q., Ohkoshi E., Li L. H., Yang L., Lee K. H., Biorg. Med. Chem. Lett., 2011, 22, 920
Liu Y. Q., Dai W., Tian J., Yang L., Feng G., Zhou X. W., Kou L., Zhao Y. L., Li W. Q., Li L. H., Heteroat. Chem., 2011, 22, 687
Liu Y. Q., Tian X., Synth. Commun., 2005, 35, 2749
Naik N., Braslau R., Tetrahedron, 1998, 54, 667
Soule B. P., Hyodo F., Matsumoto K., Simone N. L., Cook J. A., Krishna M. C., Mitchell J. B., Free Radic. Biol. Med., 2007, 42, 1632
Zakrzewski J., Krawczyk M., Heterocycl. Commun., 2014, 20, 89
Wu Y., Hirai Y., Tsunobuchi Y., Tokoro H., Eimura H., Yoshio M., Ohkoshi S., Kato T., Chem. Sci., 2012, 3, 3007
Morrison A., Davies A. P., Biol. Mass Spectrom., 1970, 3, 353
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Supported by the National Natural Science Foundation of China(No.81573315), the Natural Science Foundation of Guangdong Province, China(No.2015A030313313), the Guangzhou Industry-University Collaborative Innovation Major Projects, China(No.201508030016) and the Natural Science Foundation of Hainan Province, China(No.817307).
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Guo, J., Tan, B., Ye, Q. et al. Synthesis and cytotoxic activities of spin-labeled derivatives of Cinobufagin. Chem. Res. Chin. Univ. 33, 581–586 (2017). https://doi.org/10.1007/s40242-017-7025-x
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DOI: https://doi.org/10.1007/s40242-017-7025-x