Synthesis and biological evaluation of substituted indazolyl amide derivatives as <i>S</i>-adenosyl-L-homocysteine hydrolase inhibitors

引用本文: Xiang-Duan Tan, Li-Guang Mao, Wei Wu, Si-Yun Nian, Guo-Ping Wang. Synthesis and biological evaluation of substituted indazolyl amide derivatives as S-adenosyl-L-homocysteine hydrolase inhibitors[J]. Chinese Chemical Letters, 2016, 27(6): 984-988. doi: 10.1016/j.cclet.2016.03.028 shu

Citation: Xiang-Duan Tan, Li-Guang Mao, Wei Wu, Si-Yun Nian, Guo-Ping Wang. Synthesis and biological evaluation of substituted indazolyl amide derivatives as S-adenosyl-L-homocysteine hydrolase inhibitors[J]. Chinese Chemical Letters, 2016, 27(6): 984-988. doi: 10.1016/j.cclet.2016.03.028 shu

Synthesis and biological evaluation of substituted indazolyl amide derivatives as S-adenosyl-L-homocysteine hydrolase inhibitors

a College of Pharmacy, Guilin Medical University, Guilin 541004, China;
b Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA;
c Zhangjiang Institute, China State Institute of Pharmaceutical Industry, Shanghai 201203, China;
d Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai 201203, China
基金项目:
This research was supported by National Natural Science Foundation of China (No. 81560653) and Guangxi Natural Science Foundation of China (No. 2015GXNSFBA139124).

摘要: A series of novel amide derivatives bearing an indazole moiety were synthesized and evaluated for their in vitro S-adenosyl-L-homocysteine hydrolase (SAHase) inhibitory activity. Among these compounds, 8b, 8m, 8r and 8w showed better or similar inhibitory effects compared to the positive control aristeromycin. These results provide a novel lead for the discovery of more potent non-adenosine analogs as SAHase inhibitors.

关键词:

English

Synthesis and biological evaluation of substituted indazolyl amide derivatives as S-adenosyl-L-homocysteine hydrolase inhibitors

a College of Pharmacy, Guilin Medical University, Guilin 541004, China;
b Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA;
c Zhangjiang Institute, China State Institute of Pharmaceutical Industry, Shanghai 201203, China;
d Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai 201203, China
Received Date: 25 December 2015
Revised Date: 03 March 2016
Fund Project:
This research was supported by National Natural Science Foundation of China (No. 81560653) and Guangxi Natural Science Foundation of China (No. 2015GXNSFBA139124).

Abstract: A series of novel amide derivatives bearing an indazole moiety were synthesized and evaluated for their in vitro S-adenosyl-L-homocysteine hydrolase (SAHase) inhibitory activity. Among these compounds, 8b, 8m, 8r and 8w showed better or similar inhibitory effects compared to the positive control aristeromycin. These results provide a novel lead for the discovery of more potent non-adenosine analogs as SAHase inhibitors.

Key words:

1. [1] P.M. Ueland, Pharmacological and biochemical aspects of S-adenosylhomocysteine and S-adenosylhomocysteine hydrolase, Pharmacol. Rev. 34 (1982) 223-253.
2. [2] S. Dayal, T. Bottiglieri, E. Arning, et al., Endothelial dysfunction and elevation of Sadenosylhomocysteine in cystathionine β-synthase deficient mice, Circ. Res. 88 (2001) 1203-1209.
3. [3] I. Barić, Inherited disorders in the conversion of methionine to homocysteine, J. Inherit. Metab. Dis. 32 (2009) 459-471.
4. [4] Y. Kusakabe, M. Ishihara, T. Umeda, et al., Structural insights into the reaction mechanism of S-adenosyl-L-homocysteine hydrolase, Sci. Rep. 5 (2015) 16641.
5. [5] O. Tehlivets, N. Malanovic, M. Visram, et al., S-adenosyl-L-homocysteine hydrolase and methylation disorders: yeast as a model system, Biochim. Biophys. Acta 1832 (2013) 204-215.
6. [6] E.D. Clercq, S-adenosylhomocysteine hydrolase inhibitors as broad-spectrum antiviral agents, Biochem. Pharmacol. 36 (1987) 2567-2575.
7. [7] M.S. Wolfe, R.T. Borchardt, S-adenosyl-L-homocysteine hydrolase as a target for antiviral chemotherapy, J. Med. Chem. 34 (1991) 1521-1530.
8. [8] G. Chandra, Y.M. Moon, Y. Lee, et al., Structure-activity relationships of neplanocin A analogues as S-adenosylhomocysteine hydrolase inhibitors and their antiviral and antitumor activities, J. Med. Chem. 58 (2015) 5108-5120.
9. [9] D.M. Henderson, S. Hanson, T. Allen, et al., Cloning of the gene encoding Leishmania donovani S-adenosylhomocysteine hydrolase, a potential target for antiparasitic chemotherapy, Mol. Biochem. Parasitol. 53 (1992) 169-183.
10. [10] A. Hayden, P.W.M. Johnson, G. Packham, et al., S-adenosylhomocysteine hydrolase inhibition by 3-deazaneplanocin A analogues induces anti-cancer effects in breast cancer cell lines and synergy with both histone deacetylase and HER2 inhibition, Breast Cancer Res. Treat. 127 (2011) 109-119.
11. [11] P.K. Chiang, Biological effects of inhibitors of S-adenosylhomocysteine hydrolase, Pharmacol. Ther. 77 (1988) 115-134.
12. [12] Q.L. Wu, Y.F. Fu, W.L. Zhou, et al., Inhibition of S-adenosyl-L-homocysteine hydrolase induces immunosuppression, J. Pharmacol. Exp. Ther. 313 (2005) 705-711.
13. [13] Y.M. Zhang, Y. Ding, W. Tang, et al., Synthesis and biological evaluation of immunosuppressive agent DZ2002 and its stereoisomers, Bioorg. Med. Chem. 16 (2008) 9212-9216.
14. [14] C.S. Yuan, Y. Saso, E. Lazarides, et al., Recent advances in S-adenosyl-L-homocysteine hydrolase inhibitors and their potential clinical applications, Expert Opin. Ther. Pat. 9 (1999) 1197-1206.
15. [15] A.C. Langheinrich, R.C. Braun-Dullaeus, G. Walker, et al., Effects of 3-deazaadenosine on homocysteine and atherosclerosis in apolipoprotein E-deficient mice, Atherosclerosis 171 (2003) 181-192.
16. [16] A. Converso, T. Hartingh, M.E. Fraley, et al., Adenosine analogue inhibitors of Sadenosylhomocysteine hydrolase, Bioorg. Med. Chem. Lett. 24 (2014) 2737-2740.
17. [17] X.D. Tan, P.F. Wang, S.Y. Nian, et al., Design and synthesis of amide derivatives as S-adenosyl-L-homocysteine hydrolase inhibitors, Chem. Pharm. Bull. (Tokyo) 62 (2014) 112-117.
18. [18] A. Nakao, H. Suzuki, H. Ueno, et al., Discovery and structural analyses of Sadenosyl-L-homocysteine hydrolase inhibitors based on non-adenosine analogs, Bioorg. Med. Chem. 23 (2015) 4952-4969.
19. [19] I. Bouillon, J. Zajíček, N. Pudelova´ , et al., Remarkably efficient synthesis of 2Hindazole 1-oxides and 2H-indazoles via tandem carbon-carbon followed by nitrogen-nitrogen bond formation, J. Org. Chem. 73 (2008) 9027-9032.
20. [20] R. Parkesh, T.C. Lee, T. Gunnlaugsson, Highly selective 4-amino-1,8-naphthalimide based fluorescent photoinduced electron transfer (PET) chemosensors for Zn(II) under physiological pH conditions, Org. Biomol. Chem. 5 (2007) 310-317.
21. [21] K.I. Yoshida, K. Nakayama, N. Kuru, et al., MexAB-OprM specific efflux pump inhibitors in pseudomonas aeruginosa. Part 5. Carbon-substituted analogues at the C-2 position, Bioorg. Med. Chem. 14 (2006) 1993-2004.
22. [22] X. Huang, J. Zhu, S. Broadbent, The first asymmetric synthesis of a 4-arylsubstituted 5-carboxy-3,4-dihydropyridin-2-one derivative, Tetrahedron Lett. 51 (2010) 1554-1557.
23. [23] J.H. Lin, C.W. Chang, Z.H. Wu, et al., Colorimetric assay for S-adenosylhomocysteine hydrolase activity and inhibition using fluorosurfactant-capped gold nanoparticles, Anal. Chem. 82 (2010) 8775-8779.
24. [24] R. Hudec, K. Hamada, K. Mikoshiba, A fluorescence-based assay for the measurement of S-adenosylhomocysteine hydrolase activity in biological samples, Anal. Biochem. 433 (2013) 95-101.

扫一扫看文章

计量

PDF下载量: 1
文章访问数: 1233
HTML全文浏览量: 19

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Synthesis and biological evaluation of substituted indazolyl amide derivatives as S-adenosyl-L-homocysteine hydrolase inhibitors

English

Synthesis and biological evaluation of substituted indazolyl amide derivatives as S-adenosyl-L-homocysteine hydrolase inhibitors

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南：你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

计量

通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

Synthesis and biological evaluation of substituted indazolyl amide derivatives as S-adenosyl-L-homocysteine hydrolase inhibitors

English

Synthesis and biological evaluation of substituted indazolyl amide derivatives as S-adenosyl-L-homocysteine hydrolase inhibitors

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

计量

文章相关

通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

CCS Chemistry：颜徐州、鲍哲南：你的皮肤可能是一片SPMs