Study of antagonistic activity against M3 receptor and inhibition activity to neutrophil elastase of tropane compounds
10.3969/j.issn.1674-8115.2017.08.002
- VernacularTitle:莨菪烷类化合物拮抗M3受体、抑制中性粒细胞弹性蛋白酶活性的研究
- Author:
Yuxing CAI
;
Huizhong LIU
;
Youmin HU
;
Jianhua ZHANG
;
Yujie JIN
;
Ning LI
;
Yinyao NIU
- Keywords:
tropane;
muscarinic cholinergic receptors;
M3 receptor antagonist;
neutrophil elastase;
structure-activity relationship
- From:
Journal of Shanghai Jiaotong University(Medical Science)
2017;37(8):1059-1063
- CountryChina
- Language:Chinese
-
Abstract:
Objective · To design and synthesize five new tropane compounds, and test their antagonistic activity against M3 receptor and inhibition activity to neutrophil elastase (NE), of which the structure-activity relationship were preliminarily investigated. Methods · The five compounds, A1-A3,B1 and C1, were prepared with 3α-hydroxy-tropane (A0) as the starting material by modifying the structure in C-3α position and N atom on the tropane skeleton. The antagonistic activity of the compounds to muscarinic M3 receptors on tracheal rings of guinea pigs was evaluated by functional assays in vitro. The hydrolysis of PGlu-Pro-Val-PNA as substrate was catalyzed by NE to get colorful nitroaniline (PNA). The NE inhibition activity of the tropane compounds was obtained by determining the absorbance [(D(405 nm)] of PNA. Results · The five new tropane compounds generated strong antagonistic activity against M3 receptors. Among them, A2 had the greatest activity [antagonistic parameter pA2(M3)=9.004], and elicited obvious inhibitory effect to NE (inhibition ratio YA2=20.29%). Conclusion · Introducing strong electron-attraction group, such as sulfuryl and hydrophobic group with large volume into C-3α position on the tropane skeleton can improve the M3 receptor antagonistic activity as well as the NE inhibition activity.
