López-Corrales Marta, Marchán Vicente
Departament de Química Inorgànica i Orgànica, Secció de Química Orgànica, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona (UB), Martí i Franquès 1-11, E-08028 Barcelona, Spain.
Molecules. 2025 May 14;30(10):2158. doi: 10.3390/molecules30102158.
Photolabile protecting groups (PPGs), also known as caging groups, are valuable tools in photopharmacology. They enable precise control over the release of bioactive compounds from the corresponding caged compounds at a precisely controlled time and place using light of specific wavelengths. This study introduces a novel approach to fine-tuning the photophysical and photochemical properties of visible-light-sensitive dicyanocoumarin- and COUPY-based caging groups by incorporating a phenyl group in a position adjacent to the photolabile bond. Our photoactivation studies with visible light demonstrated that this structural modification slightly improved the photolytic efficiency of both dicyanocoumarin- and COUPY-caged model compounds compared to their methyl-substituted or unsubstituted counterparts. Furthermore, COUPY PPGs were efficiently photoactivated with red light (620 nm) and successfully used to cage two antitumor drugs, chlorambucil and 4-phenylbutyric acid. These findings highlight the potential of phenyl-containing caging groups based on dicyanocoumarin and COUPY scaffolds as versatile platforms for developing new light-activated tools for photopharmacology applications.
光不稳定保护基团（PPGs），也称为笼蔽基团，是光药理学中的重要工具。它们能够利用特定波长的光，在精确控制的时间和地点，对相应笼蔽化合物中生物活性化合物的释放进行精确控制。本研究引入了一种新方法，通过在与光不稳定键相邻的位置引入苯基，来微调基于可见光敏感的二氰基香豆素和COUPY的笼蔽基团的光物理和光化学性质。我们用可见光进行的光活化研究表明，与甲基取代或未取代的同类物相比，这种结构修饰略微提高了二氰基香豆素和COUPY笼蔽模型化合物的光解效率。此外，COUPY PPGs能用红光（620 nm）有效光活化，并成功用于笼蔽两种抗肿瘤药物，苯丁酸氮芥和4-苯基丁酸。这些发现突出了基于二氰基香豆素和COUPY支架的含苯基笼蔽基团作为开发用于光药理学应用的新型光活化工具的通用平台的潜力。
