Deuteration-Driven Photopharmacology: Deuterium-Labeled AzoCholine for Controlling Alpha 7 Nicotinic Acetylcholine Receptors

被引：3

作者：

Yang, Xingye ^{[1
,2
]}

Zhou, Xin ^{[1
]}

Qin, Xiaojun ^{[2
]}

Liang, Dong ^{[1
]}

Dong, Xuhui ^{[1
]}

Ji, Huimin ^{[1
]}

Wen, Siman ^{[2
]}

Du, Lupei ^{[1
]}

Li, Minyong ^{[1
,3
]}

机构：

[1] Shandong Univ, Cheeloo Coll Med, Sch Pharmaceut Sci, Key Lab Chem Biol,Dept Med Chem, Jinan 250012, Shandong, Peoples R China

[2] Guangxi Med Univ, Pharmaceut Coll,Guangxi Key Lab Bioact Mol Res & E, Guangxi Educ Dept,Key Lab Micro Nanoscale Bioanal, Guangxi Key Lab Pharmaceut Precis Detect & Screeni, Nanning 530021, Guangxi, Peoples R China

[3] Shandong Univ, State Key Lab Microbial Technol, Helmholtz Int Lab, Qingdao 266237, Shandong, Peoples R China

来源：

ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE | 2024年 / 7卷 / 06期

基金：

中国国家自然科学基金;

关键词：

deuteration; photopharmacology; photoswitch; alpha 7 nicotinic acetylcholine receptors; d(9)-AzoCholine; azobenzene; ALTERING METABOLIC PROFILES; IN-VIVO; PHOTOCHROMIC REAGENTS; BIOLOGICAL-ACTIVITY; ISOTOPE; AZOBENZENES; DRUG; PHOTOREGULATION; ISOMERIZATION; DISCOVERY;

D O I：

10.1021/acsptsci.4c00058

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Photopharmacology is a powerful approach to investigate biological processes and overcomes the common therapeutic challenges in drug development. Enhancing the photopharmacology properties of photoswitches contributes to extend their applications. Deuteration, a tiny structural modification, makes it possible to improve the photopharmacology and photophysical properties of prototype compounds, avoiding extra complex chemical changes or constructing multicomponent systems. In this work, we developed a series of D-labeled azobenzenes to expand the azobenzene photoswitchable library and introduced the D-labeled azobenzene unit into the photoagonist of alpha 7 nicotinic acetylcholine receptors (alpha 7 nAChRs) to investigate the effects of deuteration in photopharmacology. Spectral data indicated that deuteration maintained most of the photophysical properties of azobenzenes. The D-labeled photoagonist exhibited good control of the activity of alpha 7 nAChRs than the prototype photoagonist. These results confirmed that deuteration is a promising strategy to improve the photopharmacological properties.

引用

页码：1839 / 1846

页数：8

共 64 条

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