Syntheses and bioactivities of songorine derivatives as novel G protein-coupled receptor antagonists.

作者: Jiangming Wang , Changhao Bian , Yinan Wang , Quan Shen , Bin Bao

DOI: 10.1016/J.BMC.2019.03.045

关键词: Aconitum brachypodumG protein-coupled receptorIc50 valuesReceptorStereochemistryIn vitroChemistryDouble antibody sandwich

摘要: Abstract Songorine isolated from Aconitum brachypodum Diels possesses prominent activity of inhibiting G protein-coupled receptors (GPCRs) in the early screening process. In this paper, a series derivatives were synthesized and their inhibitory activities on GPCRs also evaluated by using Double Antibody Sandwich ELISA (DAS-ELISA) vitro. Among them, three (3a, 4, 7) exhibited significant against with IC50 values 0.08–0.29 nM. Moreover, structure-activity relationships (SARs) songorine discussed detail. They have great potentials as novel antagonists future.

参考文章(27)
Kenneth A. Jacobson, New paradigms in GPCR drug discovery Biochemical Pharmacology. ,vol. 98, pp. 541- 555 ,(2015) , 10.1016/J.BCP.2015.08.085
Hiromitsu TAKAYAMA, Feng-E WU, Hisano EDA, kyoko ODA, Norio AIMI, Shin-ichiro SAKAI, FIVE NEW NAPELLINE-TYPE DITERPENE ALKALOIDS FROM ACONITUM LIANGSHANIUM Chemical & Pharmaceutical Bulletin. ,vol. 39, pp. 1644- 1646 ,(1991) , 10.1248/CPB.39.1644
Yu. V. Nesterova, T. N. Povet’eva, N. I. Suslov, E. E. Shults, G. N. Ziuz’kov, S. G. Aksinenko, O. G. Afanas’eva, A. V. Krapivin, T. G. Kharina, Anxiolytic Activity of Diterpene Alkaloid Songorine. Bulletin of Experimental Biology and Medicine. ,vol. 159, pp. 620- 622 ,(2015) , 10.1007/S10517-015-3029-Z
Yong Shen, Ai-Xue Zuo, Zhi-Yong Jiang, Xue-Mei Zhang, Hong-Ling Wang, Ji-Jun Chen, Two New Diterpenoid Alkaloids from Aconitum brachypodum Bulletin of The Korean Chemical Society. ,vol. 31, pp. 3301- 3303 ,(2010) , 10.5012/BKCS.2010.31.11.3301
Yu. V. Nesterova, T. N. Povetieva, N. I. Suslov, G. N. Zyuz’kov, S. G. Aksinenko, S. V. Pushkarskii, A. V. Krapivin, Anti-Inflammatory Activity of Diterpene Alkaloids from Aconitum baikalense Bulletin of Experimental Biology and Medicine. ,vol. 156, pp. 665- 668 ,(2014) , 10.1007/S10517-014-2421-4
P.J. Bindu, K.M. Mahadevan, N.D. Satyanarayan, T.R. Ravikumar Naik, Synthesis and DNA cleavage studies of novel quinoline oxime esters. Bioorganic & Medicinal Chemistry Letters. ,vol. 22, pp. 898- 900 ,(2012) , 10.1016/J.BMCL.2011.12.037
Rui-Hua Guo, Quan Zhang, Yun-Bao Ma, Jie Luo, Chang-An Geng, Li-Jun Wang, Xue-Mei Zhang, Jun Zhou, Zhi-Yong Jiang, Ji-Jun Chen, Structure-activity relationships study of 6-chloro-4-(2-chlorophenyl)-3-(2-hydroxyethyl) quinolin-2(1H)-one derivatives as novel non-nucleoside anti-hepatitis B virus agents. European Journal of Medicinal Chemistry. ,vol. 46, pp. 307- 319 ,(2011) , 10.1016/J.EJMECH.2010.11.019
Mohammad F. Khan, Devendra P. Mishra, E. Ramakrishna, Arun K. Rawat, Akansha Mishra, Arvind K. Srivastava, Rakesh Maurya, Design and synthesis of lupeol analogues and their in vitro PTP-1B inhibitory activity Medicinal Chemistry Research. ,vol. 23, pp. 4156- 4166 ,(2014) , 10.1007/S00044-014-0984-2
Yong Shen, Ai-Xue Zuo, Zhi-Yong Jiang, Xue-Mei Zhang, Hong-Ling Wang, Ji-Jun Chen, Four New Nor-Diterpenoid Alkaloids from Aconitum brachypodum Helvetica Chimica Acta. ,vol. 93, pp. 863- 869 ,(2010) , 10.1002/HLCA.200900297
Quan Zhang, Zhi-Yong Jiang, Jie Luo, Yun-Bao Ma, Ji-Feng Liu, Rui-Hua Guo, Xue-Mei Zhang, Jun Zhou, Wei Niu, Fei-Fei Du, Li Li, Chuan Li, Ji-Jun Chen, None, Anti-HBV agents. Part 3: Preliminary structure–activity relationships of tetra-acylalisol A derivatives as potent hepatitis B virus inhibitors Bioorganic & Medicinal Chemistry Letters. ,vol. 19, pp. 6659- 6665 ,(2009) , 10.1016/J.BMCL.2009.10.006