Design, Synthesis and Biological Evaluation of Pyrrolo[2,1-c][1,4]benzodiazepine-3,11-dione Derivatives as Novel Neuroprotective Agents

被引：1

作者：

Quan, Jishun ^{[1
]}

Zhang, Dongping ^{[1
]}

Zhang, Zhuo ^{[1
]}

Wang, Jian ^{[1
]}

Ma, Chao ^{[1
]}

Cheng, Maosheng ^{[1
]}

机构：

[1] Shenyang Pharmaceut Univ, Sch Pharmaceut Engn, Minist Educ, Key Lab Struct Based Drug Design & Discovery, Shenyang 110016, Peoples R China

来源：

CHEMICAL RESEARCH IN CHINESE UNIVERSITIES | 2021年 / 37卷 / 03期

基金：

中国国家自然科学基金;

关键词：

Neuroprotective activity; Ca2+ influx; Western blotting; NR2B-NMDA receptor; Molecular docking; NMDA RECEPTOR ANTAGONISTS; SUBUNIT; NR2B; IFENPRODIL; POTENT;

D O I：

10.1007/s40242-020-0283-z

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Aseries of pyrrolo[2,1-c][1,4]benzodiazepine-3,11-dione derivatives was designed and synthesized, and their neuroprotective activity against SH-SY5Y cell injury induced by N-methyl-D-aspartic acid(NMDA) was evaluated. All the compounds showed significant neuroprotective effects, especially B16, which showed excellent performance and better activity than the positive control ifenprodil(B16: 56.2%+/- 0.6%; ifenprodil: 41.0%+/- 2.7%). Further investigation indicated that B16 could attenuate the Ca2+ influx induced by NMDA in SH-SY5Y cells and Western blotting also showed that B16 could attenuate the NR2B upregulation in SH-SY5Y cells induced by NMDA. The molecular docking results showed that compound B16 fitted in the binding pocket of NR2B-NMDAR well and could interact with binding sites of compounds 1 and 2 simultaneously. The ADME/Tox prediction results suggested that compound B16 had good blood-brain barrier(BBB) permeability and the zero alert of Pan Assay Interference Structures(PAINS) indicated that B16 could not elicit false-positive activities. These results strongly suggest that B16 is a promising and effective candidate neuroprotective compound, and that NR2B-NMDAR is a potential target of B16.

引用

页码：647 / 654

页数：8

共 24 条

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