Synthesis and Biological Evaluation of Tetramethylpyrazine Nitrates as Potential Anti-ischemic Stroke Agent

Xiaoquan Li; Zheng Liu; Liangmiao Wu; Zaijun Zhang; Yuqiang Wang; Yewei Sun; Pei Yu

doi:10.14233/ajchem.2016.19941

Issue

Vol. 28 No. 9 (2016): Vol 28 Issue 9

Issue Published : June 1, 2016

This work is licensed under a Creative Commons Attribution 4.0 International License.

Synthesis and Biological Evaluation of Tetramethylpyrazine Nitrates as Potential Anti-ischemic Stroke Agent

https://doi.org/10.14233/ajchem.2016.19941

Xiaoquan Li

Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University, College of Pharmacy, Guangzhou 510632, P.R. China

Zheng Liu

Liangmiao Wu

Zaijun Zhang

Yuqiang Wang

Yewei Sun

Pei Yu

Corresponding Author(s) : Pei Yu

pennypeiyu@163.com

Asian Journal of Chemistry, Vol. 28 No. 9 (2016): Vol 28 Issue 9
Article Published : June 2, 2016

Abstract

Ischemic stroke, resulting from the blockade of cerebral blood vessels, produces neuronal cell damage and death. [(3,5,6-Trimethylpyrazin-2-yl)methyl nitrate hydrochloride] (NT-1), which contains one nitrate group, was previously synthesized and shown good activity to inhibit platelet aggregation. However, NT-1’ sability to release nitric oxide (NO) and dilate blood vessels was not reported. To increase the activity of dilating cerebral blood vessels and increasing blood supply, we designed and synthesized [(3,6-dimethylpyrazine-2,5-diyl)-bis(methylene)dinitrate] (NT-2), which contains two nitrate groups. Both NT-1 and NT-2 were able to release NO in vitro and dilate the isolated rat middle cerebral artery. In addition, they protected against glutamate-induced cortical neurons damage. NT-2 was more potent than NT-1 in dilating blood vessels.

Keywords

Tetramethylpyrazine nitrate Nitric oxide Ischemic stroke

Li, X., Liu, Z., Wu, L., Zhang, Z., Wang, Y., Sun, Y., & Yu, P. (2016). Synthesis and Biological Evaluation of Tetramethylpyrazine Nitrates as Potential Anti-ischemic Stroke Agent. Asian Journal of Chemistry, 28(9), 2085–2088. https://doi.org/10.14233/ajchem.2016.19941

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K. Chen and K. Chen, Chin. Med. J. (Engl.), 105, 870 (1992).

C.-H. Li, H.-M. Liao and C.-H. Chen, Neurosci. Lett., 372, 1 (2004); doi:10.1016/j.neulet.2004.07.013.

X.-L. Zhu, L.-Z. Xiong, Q. Wang, Z.-G. Liu, X. Ma, Z.-H. Zhu, S. Hu, G. Gong and S.-Y. Chen, Neurosci. Lett., 449, 24 (2009); doi:10.1016/j.neulet.2008.09.007.

F. Tan, W. Fu, N. Cheng, D. Meng and Y. Gu, Exp. Ther. Med., 9, 1757 (2015); doi:10.3892/etm.2015.2365.

X. Zhou, L. Salganicoff and R. Sevy, Yao Xue Xue Bao, 20, 334 (1985).

S. Liu and D. Sylvester, Thromb. Res., 58, 129 (1990); doi:10.1016/0049-3848(90)90170-H.

Z.-X. Jia, Y.-S. Hu, Y. Wu, Q.-Z. Wang, N.-N. Li, Q.-C. Guo, Thromb. Res., 123, 727 (2009); doi:10.1016/j.thromres.2008.11.004.

Li Shizhen,Compendium of Materia Medica, People's Health Publishing House, Beijing (1978), China (1578).

J. Yan, Preparation of 2-hydroxymethyl-3,5,6-trimethyl-pyrazine derivatives as anticoagulants, Tian Jin Han Kang Pharmaceutical, China (2010).

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P.-N. Coneski and M.-H. Schoenfisch, Chem. Soc. Rev., 41, 3753 (2012); doi:10.1039/c2cs15271a.

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H. Chen, D. Xu, G. Tan, W. Cai, G. Zhang, W. Cui, J. Wang, C. Long, Y. Sun, P. Yu, K.W. Tsim, Z.-J. Zhang, Y.-F. Han and Y.-Q. Wang, J. Mol. Neurosci., 56, 977 (2015); doi:10.1007/s12031-015-0566-x.

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D.-P. Xu, K. Zhang, Z.-J. Zhang, Y.-W. Sun, B.-J. Guo, Y.-Q. Wang, P.-M. Hoi, Y.-F. Han and S.M.-Y. Lee, Neurochem. Int., 78, 76 (2014); doi:10.1016/j.neuint.2014.09.001.

N.M. Kaplan, Hyper., 51, 3 (2008); doi:10.1161/HYPERTENSIONAHA.107.102327.

M.-C. Seguin, F.-W. Klotz, I. Schneider, J.-P. Weir, M. Goodbary, M. Slayter, J.-J. Raney, J.-U. Aniagolu and S.-J. Green, J. Exp. Med., 180, 353 (1994); doi:10.1084/jem.180.1.353.

Issue

Vol. 28 No. 9 (2016): Vol 28 Issue 9

Synthesis and Biological Evaluation of Tetramethylpyrazine Nitrates as Potential Anti-ischemic Stroke Agent

Corresponding Author(s) : Pei Yu

Abstract

Keywords

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