Restricted suitability of BODIPY for caging in biological applications based on singlet oxygen generation
Restricted suitability of BODIPY for caging in biological applications based on singlet oxygen generation
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DOI：
10.1039/d0pp00097c
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发表时间：
2020-08
影响因子：
3.1
通讯作者：
Theo Rodat;Melanie Krebs;Alexander Döbber;B. Jansen;A. Steffen-Heins;K. Schwarz;C. Peifer
中科院分区：
文献类型：
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作者：
Theo Rodat;Melanie Krebs;Alexander Döbber;B. Jansen;A. Steffen-Heins;K. Schwarz;C. Peifer
最近的研究报告的硼-二吡咯亚甲基（BODIPY）部分是有趣的笼应用在药物药理学的基础上，其响应的照射波长在生物光学窗口。因此，在模型研究中，我们研究了内消旋-甲基-BODIPY笼状CDK 2抑制剂AZD 5438，并旨在评估BODIPY作为光可去除保护基团在光响应激酶抑制剂应用中的可用性。体外光化学分析和生物学表征揭示了BODIPY笼状抑制剂概念在水溶液中的溶解度和释放方面的显著局限性。值得注意的是，我们提供的证据BODIPY笼状化合物产生单线态氧/自由基照射后，随后通过光降解的笼状化合物系统。因此，代替笼化，细胞中坏死的非特异性诱导表明BODIPY衍生物用于光动力方法的潜在用途。
Recent studies report the boron-dipyrromethene (BODIPY) moiety to be interesting for caging applications in photopharmacology based on its response to irradiation with wavelengths in the biooptical window. Thus, in a model study, we investigated the meso -methyl-BODIPY caged CDK2 inhibitor AZD5438 and aimed to assess the usability of BODIPY as a photoremovable protecting group in photoresponsive kinase inhibitor applications. Photochemical analysis and biological characterisation in vitro revealed significant limitations of the BODIPY-caged inhibitor concept regarding solubility and uncaging in aqueous solution. Notably, we provide evidence for BODIPY-caged compounds generating singlet oxygen/radicals upon irradiation, followed by photodegradation of the caged compound system. Consequently, instead of caging, a non-specific induction of necrosis in cells suggests the potential usage of BODIPY derivatives for photodynamic approaches.