海洋天然产物Anithiactins C类似物的合成及胆碱酯酶抑制活性研究
Synthesis and Cholinesterase Inhibitory Activites of Analogues of Marine Product Anithiactins C
孙洋 1马晓冬 1邹靖培 1张笑清 1李瑞 1张钊源 1刘玮炜 1史大华2
作者信息
- 1. 江苏海洋大学药学院,江苏连云港 222005
- 2. 江苏海洋大学药学院,江苏连云港 222005;江苏海洋大学江苏省海洋生物资源与环境重点实验室,江苏连云港 222005
- 折叠
摘要
设计并合成了 3个海洋天然产物Anithiactins C类似物,利用核磁共振、X-单晶衍射技术以及红外光谱确认了化合物结构.单晶衍射结果表明,化合物2-(4-(苄氧基)苯基)-N,N-二丙基噻唑-4-甲酰胺属于三斜晶系,P-1空间群,化合物2-(4-(苄氧基)苯基)-N-环己基噻唑-4-甲酰胺属于单斜晶系,P21/c空间群.利用Ellman法检测了化合物的胆碱酯酶抑制活性,在此系列化合物中,化合物2-(4-(苄氧基)苯基)-N-环己基噻唑-4-甲酰胺表现出较好的乙酰胆碱酯酶抑制活性,IC50值为(53.99±0.13)µmol/L.分子对接结果表明该化合物同时作用于乙酰胆碱酯酶的远端阴离子结合位点和催化位点,可以作为双位点作用的乙酰胆碱抑制剂进一步开发.
Abstract
Three analogues of Marine natural product Anithiactins C were designed and synthesized.The structures of the compounds were confirmed using NMR,X-single crystal diffraction techniques and in-frared spectroscopy.The single crystal diffraction results showeded that the compound 2-(4-(benzyloxy)phenyl)-N,N-dipropylthiazole-4-carboxamide belonged to the trigonal crystal system,P-1 space group,and the compound 2-(4-(benzyloxy)phenyl)-N-cyclohexylthiazole-4-carboxamide belonged to the mono-clinic character,P21/c space group.The cholinesterase inhibitory activity of the compounds was assayed using the Ellman method,among this series,compound 2-(4-(benzyloxy)phenyl)-N-cyclohexylthiazole-4-carboxamide showed the best acetyl cholinesterase inhibitory activity with an IC50 value of(53.99±0.13)μmol/L.The molecular docking results indicated that the compound acted on both the acetyl cho-linesterase PAS and CAS sites,and could be further developed as a dual-site binding acetylcholine inhibi-tor.
关键词
Anithiactins/C类似物/合成/表征/胆碱酯酶抑制活性Key words
analogue of Anithiactins C/synthesis/characterization/cholinesterase inhibitory activites引用本文复制引用
基金项目
江苏高校优势学科建设工程项目(PAPD)()
出版年
2024
NETL
NSTL
万方数据