Synthesis, Characterization and Antidiabetic Activities of Novel Genipin Derivatives

doi:10.7503/cjcu20130284

Abstract

Abstract:

Diabetes has become the third major diseases threat to human's health and safety after cancer, cardiovascular and cerebrovascular diseases. The currently used drugs are difficult to completely cure the disease, and the long-term use is easy to produce side effects and drug resistance. So, it is very important to research and development a new kind of drug to treat the diabetes. The extract of gardenia and fruit containing the active ingredient genipin showed a very good effect in the traditional Chinese medicine treating the diabetes. In order to find novel anti-diabebes molecules, two core compounds containing amine group were synthesized from the commercial available genipin by methylation(benzylation), substitution with methylsulfonyl chloride followed by sodium azide and reduction. Thirteen novel compounds were obtained by reacting the two core compounds with a variety of acyl chlorides. The total yields were between 41% and 63%. Their structures were characterized by NMR, ESI-MS and elemental analysis and anti-dibiatic activities were evaluated by DPP Ⅳ assay at a concentration of 10 mmol/L. The results showed that all the title compounds exhibited certain extent inhibitory activities against DPP Ⅳ. Among them, compound 10f showed higher inhibitory rate up to 31.2%.

Key words: Diabetes, Genipin, Inhibitor

CLC Number:

O621.3

TrendMD:

LI Zhi-Wei, BAO Zhi-Chao, WANG Jian-Nan, CAO Rui-Feng, XIE Zhao-Yang, ZHENG Qun-Yi. Synthesis, Characterization and Antidiabetic Activities of Novel Genipin Derivatives[J]. Chem. J. Chinese Universities, 2013, 34(12): 2752.

References

[1] Niu J., Pi Z. F., Yue H., Liu S. Y., Chem. J. Chinese Universities, 2012, 33(10), 2169—2172(牛俊, 皮子凤, 越皓, 刘淑莹. 高等学校化学学报, 2012, 33(10), 2169—2172)

[2] Chan C., De L., Joseph J., McQuaid T., Ha X., Xu F., Tsushima R., Pennefather P., Salapatek A., Wheeler M., Diabetes, 2001, 50, 1302—1310

[3] Krauss S., Zhang C., Lowell B., Proc. Natl. Acad. Sci., 2002, 99, 118—122

[4] Fu C. S., Luo H. X., Zhang X. S., World Notes Plant Med., 2004, 19(4), 152—156(傅春升, 娄红祥, 张学顺. 国外医药.植物药分册, 2004, 19(4), 152—156)

[5] Huang H. L., Yang H. J., Liu L. C., Qiu Y. W., Liu J., Ding K., Tradit. Chin. Drug Res. Pharmacol, 2006, 17(1), 1—3(黄洪林, 杨怀瑾, 刘立超, 邱咏薇, 刘杰, 丁舸. 中药新药与临床药理, 2006, 17(1), 1—3)

[6] Shi H. Y., He X., Ouyang D. S., Zhou H. H., Chin. Pharm. J., 2006, 41(1), 4—6(史卉妍, 何鑫, 欧阳东升, 周宏灏. 中国药学杂志, 2006, 41(1), 4—6)

[7] Zhao Y. N., Zhang W. M., Qian Y., Zhao B. T., Chin. Wild Plant Resources, 2011, 30(1), 1—5(赵亚南, 张卫明, 钱骅, 赵伯涛. 中国野生植物资源, 2011, 30(1), 1—5)

[8] Yan J. E., Li W. C., LÜ Q. J., Bian G. X., Wen L. Q., Ren J. P., J. Sichuan Agric. Sci. Tech., 2007, 25(4), 415—418(颜静恩, 李晚忱, 吕秋军, 卞广兴, 温利青, 任建平. 四川农业大学学报, 2007, 25(4), 415—418)

[9] Zhang C., Parton L., Ye C., Krauss S., Shen R., Lin C., Porco J., Lowell B., Cell Metab., 2006, 3, 417—427

[10] Zhang C., Lowell B., Porco J., Shen R., Lin C., Krauss S., Genipin Derivatives and Uses Thereof, US 20080009450, 2008-01-10

[11] Liang Y., Yu D. Z., Chin. J. Org. Chem., 2011, 31(8), 1324—1333(梁英, 喻大昭. 有机化学, 2011, 31(8), 1324—1333) 

[12] Zou M., Lu J. R., Chen H. P., Chem. J. Chinese Universities, 2012, 33(10), 2235—2238(邹敏, 卢俊瑞, 陈慧平.高等学校化学学报, 2012, 33(10), 2235—2238)

[13] Liu D., Zhu X. J., Jiang M., Chen H., Lan S. P., Chem. J. Chinese Universities, 2012, 33(10), 2249—2255(刘丹, 朱秀杰, 姜梦, 陈虹, 兰帅鹏. 高等学校化学学报, 2012, 33(10), 2249—2255)

[14] Xu Y., Xue S. J., Chem. Res. Chinese Universities, 2009, 25(6), 846—850

[15] Hu G. Q., Wang G. Q., Duan N. N., Wen X. Y., Cao T. Y., Xie S. Q., Huang W. L., Chem. Res. Chinese Universities, 2012, 28(6), 980—984

[16] Huang Z., Luo J., Chen H. R., Yao X. S., Chin. J. Med. Chem., 2011, 21(3), 204—207(黄照, 罗军, 陈河如, 姚新生. 中国药物化学杂志, 2011, 21(3), 204—207)

[17] Moon S., Choi H., Lee S., Chung J., Ha J., Lee K., Oh S., Jeong K., Genipin Derivative Having Liver Protection Activity, US 6262083, 2001-07-17

[18] Moon S., Choi H., Lee S., Chung J., Kim J., Chung D., Park M., Cho I., Choi K., Novel Genipin Derivative Having Anti Hepatitis B Virus Activity, WO 98/17663, 1998-04-30

[19] Farilla L., Bulotta A., Hirshberg B., Endocrinology, 2003, 144(12), 5149—5158

[20] Strop P., Bankovich A. J., Hansen K.C., Garcia K.C., Brunger A. T., J. Mol. Biol., 2004, 343(4), 1055—1065