期刊
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
卷 35, 期 1, 页码 478-488出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/14756366.2019.1710501
关键词
Acetylcholinesterase; butyrylcholinesterase; organophosphate; reactivator; oxime
资金
- Czech Science Foundation [18-01734S]
- University of Hradec Kralove [Faculty of Science) [SV2113-2019, VT2019-2021]
- Ministry of Education, Youth and Sports of the Czech Republic [project ERDF] [CZ.02.1.01/0.0/0.0/18_069/0010054]
- MH CZ - DRO [University Hospital Hradec Kralove] [00179906]
- Faculty of Military Health Sciences (Long-term development plan)
- National Grid Infrastructure MetaCentrum programme under the Projects of Large Research, Development, and Innovations Infrastructures [CESNET LM2015042]
The series of symmetrical and unsymmetrical isoquinolinium-5-carbaldoximes was designed and prepared for cholinesterase reactivation purposes. The novel compounds were evaluated for intrinsic acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) inhibition, when the majority of novel compounds resulted with high inhibition of both enzymes and only weak inhibitors were selected for reactivation experiments on human AChE or BChE inhibited by sarin, VX, or paraoxon. The AChE reactivation for all used organophosphates was found negligible if compared to the reactivation ability of obidoxime. Importantly, two compounds were found to reactivate BChE inhibited by sarin or VX better to obidoxime at human attainable concentration. One compound resulted as better reactivator of NEMP (VX surrogate)-inhibited BChE than obidoxime. The in vitro results were further rationalized by molecular docking studies showing future directions on designing potent BChE reactivators.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据