Synthesis and Cytotoxic Activities of Spin-labeled Derivatives of Cinobufagin

doi:10.1007/s40242-017-7025-x

Chemical Research in Chinese Universities ›› 2017, Vol. 33 ›› Issue (4): 581-586.doi: 10.1007/s40242-017-7025-x

• Articles • Previous Articles Next Articles

Synthesis and Cytotoxic Activities of Spin-labeled Derivatives of Cinobufagin

GUO Jinhua¹, TAN Bei¹, YE Qingmei³, LIANG Guangping¹, YI Min¹, JIANG Renwang^1,2

1. Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, P. R. China;
2. Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, P. R. China;
3. Department of Pharmacy, Hainan General Hospital, Haikou 570311, P. R. China

Received:2017-01-16 Revised:2017-05-02 Online:2017-08-01 Published:2017-05-15
Contact: JIANG Renwang E-mail:trwjiang@jnu.edu.cn
Supported by:
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）.

Abstract

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.

Key words: Cinobufagin, Nitroxyl free radical, Spin-labeled, Cytotoxic activity

GUO Jinhua, TAN Bei, YE Qingmei, LIANG Guangping, YI Min, JIANG Renwang. Synthesis and Cytotoxic Activities of Spin-labeled Derivatives of Cinobufagin[J]. Chemical Research in Chinese Universities, 2017, 33(4): 581-586.

References

[1] World Health Organization, World Cancer Day-"Together It Is Possible", http://www.who.int/cancer/en/[2012-03-30]
[2] Tan Y. F., Sun X. H., Dong F. Y., Tian H. Y., Jiang R. W., Chin. J. Chem., 2015, 33, 1084
[3] Chen Q., Lin J. H., Zhao D., Zhu X., Chem. Res. Chinese Universities, 2016, 32(4), 792
[4] Hong Z., Chan K., Yeung H. W., J. Pharm. Pharmacol., 1992, 44, 1023
[5] Wang J., Jin W., Jin H., Zhou F., China Journal of Chinese Materia Medica, 1998, 23, 651
[6] Yeh J. Y., Huang W. J., Kan S. F., Wang P. S., The Prostate, 2003, 54, 112
[7] Wang L., Wu J., Li M., Yang X. W., Cui J. R., Chin. J. Oncol., 2006, 27, 717
[8] 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
[9] Ye M., Ning L. L., Zhan J. X., Guo H. Z., Guo D. A., Journal of Molecular Catalysis B, Enzymatic, 2003, 22, 89
[10] Zhou M. Q., Hou Y. P., Hamza A., Zhan C. G., Bugni T. S., Thorson J. S., Org. Lett., 2012, 14, 5424
[11] Jin Y., Chen S. W., Tian X., Biorg. Med. Chem., 2006, 14, 3062
[12] Gadjeva V. G., Int. J. Pharm., 2002, 247, 39
[13] Jing X. H., Zhang J. Q., Zhang Z. W., Tian X., Chem. Res. Chinese Universities, 2010, 26(5), 753
[14] Yang L., Liu Y. Q., Tan H., Li W. G., Tian X., Nat. Prod. Res., 2007, 21, 998
[15] 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
[16] Liu Y. Q., Ohkoshi E., Li L. H., Yang L., Lee K. H., Biorg. Med. Chem. Lett., 2011, 22, 920
[17] 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
[18] Liu Y. Q., Tian X., Synth. Commun., 2005, 35, 2749
[19] Naik N., Braslau R., Tetrahedron, 1998, 54, 667
[20] 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
[21] Zakrzewski J., Krawczyk M., Heterocycl. Commun., 2014, 20, 89
[22] Wu Y., Hirai Y., Tsunobuchi Y., Tokoro H., Eimura H., Yoshio M., Ohkoshi S., Kato T., Chem. Sci., 2012, 3, 3007
[23] Morrison A., Davies A. P., Biol. Mass Spectrom., 1970, 3, 353

Synthesis and Cytotoxic Activities of Spin-labeled Derivatives of Cinobufagin

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 10

Recommended Articles

Metrics

Comments

[1]	WU Qian, JIN Yongri, YAO Hua, LIU Ying, LI Peng, LI Xuwen. Two New Baccharane Glycosides from Seeds of Impatientis balsamina L. with in vitro Growth Inhibitory Activity in Human Cancer A375 Cells [J]. Chemical Research in Chinese Universities, 2017, 33(5): 753-757.
[2]	LIANG Guangping, CHUNG Tseyu, GUO Jinhua, ZHANG Rongrong, XÜ Wei, TZEN Jason T. C., JIANG Renwang. Novel Cinobufagin Oxime Ether Derivatives as Potential Na⁺/K⁺-ATPase Inhibitors: Synthesis, Biological Screening and Molecular Docking [J]. Chemical Research in Chinese Universities, 2017, 33(3): 378-383.
[3]	HOU Yunlei, WU Shasha, MA Longsheng, BAI Jinying, LIU Zijian, ZHAO Yanfang. Design, Synthesis and Antitumor Activity of Novel 6,7-Dimethoxyquinazoline Derivatives Containing Diaryl Urea Moiety [J]. Chemical Research in Chinese Universities, 2015, 31(5): 766-773.
[4]	HU Hao, JIANG Mingyan, XIE Lijun, HU Gang, ZHANG Cuirong, ZHANG Lixia, ZHOU Shunguang, ZHANG Meihui, GONG Ping. Design, Synthesis and Pharmacological Evaluation of Novel 4-Phenoxyquinoline Derivatives as Potential Antitumor Agents [J]. Chemical Research in Chinese Universities, 2015, 31(5): 746-755.
[5]	SU Ran, LÜ Lei, ZHENG Songzhi, JIN Yinghua, AN Shengji. Synthesis and Characterization of Novel Azo-containing or Azoxy-containing Schiff Bases and Their Antiproliferative and Cytotoxic Activities [J]. Chemical Research in Chinese Universities, 2015, 31(1): 60-64.
[6]	CHEN Jiawen, XU Lin, SUN Shiyang, ZHANG Huafei, MA Tonghui, SU Weiheng, JIANG Chunlai. Identification of Cinobufagin and Resibufogenin as Inhibitors of Enterovirus 71 Infection [J]. Chemical Research in Chinese Universities, 2014, 30(6): 953-958.
[7]	SONG Kaizhen, MA Junjie, WANG Xiao, GONG Ping, ZHAO Yanfang. Synthesis and Antitumor Activities of Novel 4-Morpholinothieno[3,2-d]pyrimidine Derivatives [J]. Chemical Research in Chinese Universities, 2014, 30(1): 75-81.
[8]	HAN Tian-jiao, WANG Qing, SONG Feng-rui, LIU Zhong-ying, LIU Zhi-qiang*,.... Intestinal Transport and Biotransformation of Resibufogenin and Cinobufagin in Chan Su via HPLC/APCI-MSn [J]. Chemical Research in Chinese Universities, 2011, 27(3): 380-384.
[9]	LIAO Xiao-jian, TANG Li-dan, LIANG Yuan-wei, GENG Hua-wei and XU Shi-hai*. Isolation and Identification of Two New Polyhydroxylated Sterols from Soft Coral Sinularia sp. [J]. Chemical Research in Chinese Universities, 2011, 27(2): 217-220.
[10]	ZHANG Xing, WU Jiao, HAN Zhuang, MEI Wen-li* and DAI Hao-fu*. Antioxidant and Cytotoxic Phenolic Compounds of Areca Nut(Areca catechu) [J]. Chemical Research in Chinese Universities, 2010, 26(1): 161-164.