Syntheses of Lactam Derivatives of Chenodeoxycholic Acid and in vitro Antiproliferative Activity

doi:10.1007/s40242-014-4003-4

高等学校化学研究 ›› 2014, Vol. 30 ›› Issue (4): 605-613.doi: 10.1007/s40242-014-4003-4

Syntheses of Lactam Derivatives of Chenodeoxycholic Acid and in vitro Antiproliferative Activity

HUANG Yanmin¹, YAO Qiucui¹, CUI Jianguo¹, GAN Chunfang¹, HUANG Qianyang¹, SU Bing², ZHOU Aimin²

1. College of Chemistry and Life Science, Guangxi Teachers Education University, Nanning 530001, P. R. China;
2. Department of Chemistry, Clevel and State University, Cleveland, OH 44115, USA

出版日期:2014-08-01 发布日期:2014-03-05
通讯作者: CUI Jianguo, ZHOU Aimin E-mail:cuijg1954@126.com;a.zhou@csuohio.edu
基金资助:
Supported by the Natural Science Foundation of Guangxi Province of China(No.2010GXNSFD013019), the Natural Science Fund of Education Department of Guangxi Province of China(No.201202ZD059) and the Training Project for Excellent Middle-aged/Young Teachers in Guangxi Higher Education Institutions of China.

Syntheses of Lactam Derivatives of Chenodeoxycholic Acid and in vitro Antiproliferative Activity

HUANG Yanmin¹, YAO Qiucui¹, CUI Jianguo¹, GAN Chunfang¹, HUANG Qianyang¹, SU Bing², ZHOU Aimin²

1. College of Chemistry and Life Science, Guangxi Teachers Education University, Nanning 530001, P. R. China;
2. Department of Chemistry, Clevel and State University, Cleveland, OH 44115, USA

Online:2014-08-01 Published:2014-03-05
Contact: CUI Jianguo, ZHOU Aimin E-mail:cuijg1954@126.com;a.zhou@csuohio.edu
Supported by:
Supported by the Natural Science Foundation of Guangxi Province of China(No.2010GXNSFD013019), the Natural Science Fund of Education Department of Guangxi Province of China(No.201202ZD059) and the Training Project for Excellent Middle-aged/Young Teachers in Guangxi Higher Education Institutions of China.

摘要/Abstract

摘要：

With chenodeoxycholic acid as starting material, a series of lactam derivatives of chenodeoxycholic acid was synthesized and their antiproliferative activities against some cancer cells were determined. Among the synthesized derivatives, compounds 6 and 18 displayed distinct antiproliferative activity against PC-3, H-292, SKBR3 and Hey-1B cancer cells, and compounds 10, 17 and 18 showed significant antiproliferative activity against SKBR3 cells. Our results reveal that the position of hydroximino on ring A or B of the parental scaffold dramatically affects the antiproliferative activity of these compounds. The conversion of 7-hydroximino to other substituent or 7-hydroximino to 3-hydroximino in the compounds resulted in a dramatic decrease of the antiproliferative activity, suggesting the importance of 7-hydroximino group for the biological activity of the compounds. The structure/activity correlation generated from the studies provides valuable information for the further design of novel chemotherapeutic drugs.

关键词: Steroidal lactam, Chenodeoxycholic acid, Antiproliferative activity

Abstract:

Key words: Steroidal lactam, Chenodeoxycholic acid, Antiproliferative activity

HUANG Yanmin, YAO Qiucui, CUI Jianguo, GAN Chunfang, HUANG Qianyang, SU Bing, ZHOU Aimin. Syntheses of Lactam Derivatives of Chenodeoxycholic Acid and in vitro Antiproliferative Activity[J]. 高等学校化学研究, 2014, 30(4): 605-613.

参考文献

[1] Czaja M. J., Am. J. Physiol. Gastrointest. Liver Physiol., 2003, 284, G875
[2] Martinez J. D., Stratagoules E. D., LaRue J. M., Powell A. A., Gause P. R., Craven M. P., Marianne B. P., Eugene W. G., David L. E., Nutr. Cancer, 1998, 31, 111
[3] Faubion W. A., Guicciardi M. E., Miyoshi H., Bronk S. F., Roberts P. J., Svingen P. A. Kaufmann S. K., Gores G. J., J. Clin. Invest., 1999, 103, 137
[4] Sodeman T., Bronk S. F., Roberts P. J., Miyoshi H., Gores G. J., Am. J. Physiol. Gastrointest. Liver Physiol., 2000, 278, G992
[5] Im E. O., Choi Y. H., Paik K. J., Suh H., Jin Y., Kim K. W., Yoo Y. H., Kim N. D., Cancer Lett., 2001, 163, 83
[6] Choia Y. H., Im E. O., Suh H., Jin Y., Yoo Y. H., Kim N. D., Cancer Lett., 2003, 199, 157
[7] Brossard D., Kihel L. E., Clément M., Sebbahi W., Khalid M., Roussakis C., Rault S., Europ. J. Med. Chem., 2010, 45 , 2912
[8] Rasras A. J. M., Al-Tel T. H., Al-Aboudi A. F., Al-Qawasmeh R. A., Europ. J. Med. Chem., 2010, 45, 2307
[9] Siless G. E., Knott M. E., Derita M. G., Zacchino S. A., Puricelli L., Palermo J. A., Steroids, 2012, 77, 45
[10] Zhang J. L., Wang H., Pi H. F., Ruan H. L., Zhang P., Wu J. Z., Steroids, 2009, 74, 424
[11] Liang D., Zhou Q., Zhang J. L., Gong W., Xu C. R., Li B., Wang Y., Li J. T., Steroids, 2012, 77, 1381
[12] Dimitrios T. P. T., Cancer Lett., 2006, 243, 202
[13] Natalija M. K., Mira S. B., ?eljko ?., Mirjana D. P., Zorica D. J., Vladimir D. P., Steroids, 2007, 72, 406
[14] Anna I. K., Manolis A. F., Evagelia S. A., Athanasios P., George N. P., Sotiris S. N., Bioorg. Med. Chem., 2008, 16, 5207
[15] Dimitrios T. P. T., George D. G., Catherine K., Athanasios P., Panayiotis K., Charalambos C., Breast Can. Res. Treat., 2006, 97, 17
[16] Huang Y. M., Chen S. J., Cui J. G., Gan C. F., Liu Z. P., Wei Y. L., Song H. C., Steroids, 2011, 76, 690
[17] Huang Y. M., Cui J. G., Zhong Z. G., Gan C. F., Zhang W. Y., Song H. C., Bioorg. Med. Chem. Lett., 2011, 21, 3641
[18] Huang Y. M., Cui J. G., Chen S. J., Gan C. F., Zhou A. M., Steroids, 2011, 76, 1346
[19] Huang Y. M., Cui J. G., Zeng Q. X., Zeng C., Chen Q., Zhou A. M., Steroids, 2012, 77, 829
[20] Chen S. J., Zhang X. J., Jia L. Y., Cui J. G., Chem. Res. Appl., 2010, 22, 848
[21] Lama R., Zhang L., Naim J. M., Williams J., Zhou A., Su B., Bioorg. Med. Chem., 2013, 21, 922

Syntheses of Lactam Derivatives of Chenodeoxycholic Acid and in vitro Antiproliferative Activity

Syntheses of Lactam Derivatives of Chenodeoxycholic Acid and in vitro Antiproliferative Activity

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