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[1]陈佳丽,等.亚氨基哒嗪类衍生物对人与昆虫GABA受体的选择性研究[J].武汉工程大学学报,2019,(01):12-18.[doi:10. 3969/j. issn. 1674?2869. 2019. 01. 002]
　CHEN Jiali,ZHAI Na,CHEN Da,et al.Selectivity of Iminopyridazine Derivatives for GABA Receptors in Human Being and Insects[J].Journal of Wuhan Institute of Technology,2019,(01):12-18.[doi:10. 3969/j. issn. 1674?2869. 2019. 01. 002]
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亚氨基哒嗪类衍生物对人与昆虫GABA受体的选择性研究(/HTML)
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《武汉工程大学学报》[ISSN:1674-2869/CN:42-1779/TQ]

卷:
期数:
2019年01期
页码:
12-18
栏目:
化学与化学工程
出版日期:
2019-03-23

文章信息/Info

Title:
Selectivity of Iminopyridazine Derivatives for GABA Receptors in Human Being and Insects
文章编号:
20190102
作者:
陈佳丽1;  2; 翟　纳1; 2; 陈　达1; 2; 王秀美1; 2; 田亚锋1; 2; 郑小娇1; 2; 刘根炎*1; 2
1. 武汉工程大学化工与制药学院，湖北 武汉 430205；2. 绿色化工过程教育部重点实验室（武汉工程大学），湖北 武汉 430205
Author(s):
CHEN Jiali1; 2; ZHAI Na1; 2; CHEN Da1; 2; WANG Xiumei1; 2; TIAN Yafeng1; 2;  ZHENG Xiaojiao1; 2;  LIU Genyan*1; 2
1. School of Chemical Engineering and Pharmacy，Wuhan Institute of Technology，Wuhan 430205， China；2. Key Laboratory of Green Chemical Process （Wuhan Institute of Technology） ，Ministry of Education，Wuhan 430205， China
关键词:
GABA受体; 竞争性拮抗剂; 亚氨基哒嗪类衍生物; 分子对接; 选择性
Keywords:
GABA receptor;  competitive antagonists;  iminopyridazine derivatives;  molecular docking;  selectivity
分类号:
S482.3
DOI:
10. 3969/j. issn. 1674?2869. 2019. 01. 002
文献标志码:
A
摘要:
摘　要： 通过同源模建的方法构建了三种昆虫（家蝇、褐飞虱和斜纹夜蛾）的离子型GABA受体模型和人的α1β2γ2 GABA受体模型，并经能量优化、动力学模拟和拉氏图分析验证了所建模型的稳定性与合理性。将GABA受体竞争性拮抗剂亚氨基哒嗪类衍生物分别与所构建模型进行分子对接研究其作用机理，结果表明，亚氨基哒嗪类衍生物在昆虫模型中的对接打分与生物活性测试结果基本吻合，其与三种昆虫GABA受体的结合模式较人的GABA受体具有差异性和选择性。从分子层面预测和解释了昆虫GABA受体竞争性拮抗剂的选择性作用机理，为研发高效、安全的新靶点杀虫剂提供了理论依据和新思路。
Abstract:
The ionotropic GABA receptor （GABAR） models of three kinds of insects （Musca domestica， Laodelphax striatellus and Spodopteralitura） and the α1β2γ2 GABAR model for human being were constructed by homology modeling. The stability and rationality of these models were verified by energy optimization， dynamic simulation， and Ramachandran graph analysis. The docking mechanisms of iminopyridazine derivatives as competitive antagonists of GABARs into the constructed models were investigated. The results indicated that the docking scores of the iminopyridazines in GABAR models of the insects were generally consistent with their bioactivities， while the binding patterns of iminopyridazines in GABARs of human being and insect were different. This study predicted and explained the selectivity of competitive antagonists of insect GABARs at the molecular level and the docking mechanism， providing the theoretical basis and new ideas for the development of new target insecticides with high efficiency and safety.

参考文献/References:

［1］　CHUA H C，CHEBIB M. GABAA receptors and the diversity in their structure and pharmacology［J］. Advances in Pharmacology，2017，79：1-34. ［2］　HEANEY C F，KINNEY J W. Role of GABAB receptors in learning and memory and neurological disorders［J］. Neuroscience & Biobehavioral Reviews，2016，63：1-28. ［3］　CASIDA J E， DURKIN K A. Novel GABA receptor pesticide targets［J］. Pesticide Biochemistry & Physiology，2015，121：22-30. ［4］　BUCKINGHAM SD，IHARA M，SATTELLE DB，et al.Mechanisms of action， resistance and toxicity ofinsecticides targeting GABA receptors［J］. Current Medicinal Chemistry，2017，24（27）：2935-2945. ［5］　MILLER P S， SMART T G. Binding， activation and modulation of Cys-loop receptors［J］. Trends in Pharmacological Sciences，2010，31（4）：161-174. ［6］　MILLER P S， ARICESCU A R. Crystal structure of a human GABAA receptor［J］. Nature，2014，512（7514）：270-275. ［7］　BLOOMQUIST J R. Chloride channels as tools for developing selective insecticides［J］. Archives of Insect Biochemistry & Physiology，2003，54（4）：145-156. ［8］　FFRENCH-CONSTANT R H，WILLIAMSON M S，DAVIESTGE，et al. Ion channels as insecticide targets［J］. Journal of Neurogenetics，2016，30：163-177. ［9］　THOMPSON M，STEICHEN J C，FFRENCH- CONSTANT R H. Conservation of cyclodiene insecticide resistance-associated mutations in insects［J］. Insect Molecular Biology，2010，2（3）：149-154. ［10］　NAKAO T. Mechanisms of resistance to insecticides targeting RDL GABA receptors in planthoppers［J］. Neurotoxicology，2016，60（2）：293-298. ［11］　郑小娇，李华光，刘根炎，等. 昆虫γ-氨基丁酸受体竞争性拮抗剂的研究进展［J］. 农药学学报，2017，19（6）：665-671. ［12］　WERMUTH C G， BOURGUIGNON J J， SCHLEWER G，et al. Synthesis and structure-activity relationships of a series of aminopyridazine derivatives of γ-aminobutyric acid acting as selective GABAA antagonists［J］. Journal of Medicinal Chemistry，1987，30（2）：239-249. ［13］　JOHNSTON G A. Advantages of an antagonist： bicuculline and other GABA antagonists［J］. British Journal of Pharmacology，2013，169（2）：328-336. ［14］　LIU G，OZOE F， FURUTA K， et al. 4，5-Substituted 3-isoxazolols with insecticidal activity act as competitive antagonists of housefly GABA receptors［J］. Journal of Agricultural and Food Chemistry，2015，63（28）：6304-6312. ［15］　LIU G，FURUTA K，NAKAJIMA H， et al. Competitive antagonism of insect GABA receptors by 4-substituted 5-（4-piperidyl）-3-isothiazolols ［J］. Bioorganic & Medicinal Chemistry，2014，22（17）：4637-4645. ［16］　RAHMAN M M， AKIYOSHI Y， FURUTANI S， et al. Competitive antagonism of insect GABA receptors by iminopyridazine derivatives of GABA［J］. Bioorganic & Medicinal Chemistry，2012，20（19）：5957-5964. ［17］　RAHMAN M M， LIU G， FURUTA K， et al. Synthesis of 1，3-di- and 1，3，4-trisubstituted 1，6-dihydro-6-iminopyridazines as competitive antagonists of insect GABA receptors［J］. Journal of Pesticide Science，2014，39（3）：133-143. ［18］　SANDER T， FR?LUND B， BRUUN A T， et al. New insights into the GABAA receptor structure and orthosteric ligand binding： receptor modeling guided by experimental data［J］. Proteins Structure Function & Bioinformatics，2011，79（5）：11458-11477. ［19］　KRALL J， JENSEN C H， S?RENSEN T E， et al. Exploring the orthosteric binding site of the γ-aminobutyric acid type A receptor using 4-（piperidin-4-yl）-1-hydroxypyrazoles 3- or 5-imidazolyl substituted： design， synthesis， and pharmacological evaluation［J］. Journal of Medicinal Chemistry，2013，56（16）：16536-16540. ［20］　LIU G， FR?LUND B， OZOE F，et al. Differential interactions of 5-（4-piperidyl）-3-isoxazolol analogues with insect γ-aminobutyric acid receptors leading to functional selectivity［J］. Insect Biochemistry and Molecular Biology，2015，66：64-71.Synthesis, Crystal Structure and Thermal Stability of Copper Complex of 1,3-Propane Diamine

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备注/Memo

备注/Memo:
收稿日期：2018-09-20基金项目：国家自然科学基金（21807082）；湖北省自然科学基金（2017CFB121）；湖北省教育厅科学技术研究项目（Q20171503）；武汉工程大学大学生校长基金（2018006）作者简介：陈佳丽，本科生。E-mail：[email protected]*通讯作者：刘根炎，博士，特聘教授，硕士研究生导师。E-mail：[email protected]引文格式：陈佳丽，翟纳，陈达，等. 亚氨基哒嗪类衍生物对人与昆虫GABA受体的选择性研究［J］. 武汉工程大学学报，2019，41（1）：12-18，24.
更新日期/Last Update: 2019-02-18