Yang Xingye, Zhou Xin, Qin Xiaojun, Liang Dong, Dong Xuhui, Ji Huimin, Wen Siman, Du Lupei, Li Minyong
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
Pharmaceutical College, Guangxi Key Laboratory of Pharmaceutical Precision Detection and Screening, Key Laboratory of Micro-Nanoscale Bioanalysis and Drug Screening of Guangxi Education Department, Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, Guangxi Medical University, Nanning, Guangxi 530021, China.
ACS Pharmacol Transl Sci. 2024 May 10;7(6):1839-1846. doi: 10.1021/acsptsci.4c00058. eCollection 2024 Jun 14.
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 α7 nicotinic acetylcholine receptors (α7 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 α7 nAChRs than the prototype photoagonist. These results confirmed that deuteration is a promising strategy to improve the photopharmacological properties.
光药理学是研究生物过程的一种有力方法，克服了药物开发中常见的治疗挑战。增强光开关的光药理学性质有助于扩展其应用。氘代作为一种微小的结构修饰，能够改善原型化合物的光药理学和光物理性质，避免额外复杂的化学变化或构建多组分体系。在这项工作中，我们开发了一系列氘标记的偶氮苯以扩展偶氮苯光开关库，并将氘标记的偶氮苯单元引入α7烟碱型乙酰胆碱受体（α7 nAChRs）的光激动剂中，以研究氘代在光药理学中的作用。光谱数据表明，氘代保留了偶氮苯的大部分光物理性质。与原型光激动剂相比，氘标记的光激动剂对α7 nAChRs的活性表现出更好的控制。这些结果证实，氘代是改善光药理学性质的一种有前景的策略。
