1. Academic Validation
  2. Synthesis and biological evaluation of memantine nitrates as a potential treatment for neurodegenerative diseases

Synthesis and biological evaluation of memantine nitrates as a potential treatment for neurodegenerative diseases

  • Medchemcomm. 2016 Oct 20;8(1):135-147. doi: 10.1039/c6md00509h.
Zheng Liu 1 Si Yang 1 Xiaoyong Jin 1 Gaoxiao Zhang 1 Baojian Guo 1 Haiyun Chen 1 Pei Yu 1 Yewei Sun 1 Zaijun Zhang 1 Yuqiang Wang 1
Affiliations

Affiliation

  • 1 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 , China . Email: yxy0723@163.com ; Email: zaijunzhang@163.com ; ; Tel: +86 20 8522 5030.
Abstract

A series of memantine nitrate derivatives, as dual functional compounds with neuroprotective and vasodilatory activity for neurodegenerative diseases, was designed and synthesized. These compounds combined the memantine skeleton and a nitrate moiety, and thus inhibited the N-methyl-d-aspartic acid receptor and released NO in the central nervous system. The biological evaluation results revealed that the new memantine nitrates were effective in protecting neurons against glutamate-induced injury in vitro. Moreover, memantine nitrates dilated aortic rings against phenylephrine-induced contraction. The structure-activity relationships of neuroprotection and vasodilation were both analyzed. In further studies, compound MN-05 significantly protected cortical neurons by inhibiting CA2+ influx, reducing free radical production and maintaining the mitochondrial membrane potential. Further research on MN-05 is warranted.

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