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Synthesis and Photodynamic Activities of Pyridine- or Pyridinium-Substituted Aza-BODIPY Photosensitizers
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2024-08-21 , DOI: 10.1021/acs.jmedchem.4c01641 Chang Liu 1 , Chuan Liu 1 , Xin Ji 1 , Weili Zhao 1 , Xiaochun Dong 1
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2024-08-21 , DOI: 10.1021/acs.jmedchem.4c01641 Chang Liu 1 , Chuan Liu 1 , Xin Ji 1 , Weili Zhao 1 , Xiaochun Dong 1
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In this work, various novel pyridinyl- and pyridinium-modified Aza-BODIPY PSs were designed and constructed based on monoiodo Aza-BODIPY PSs (BDP-4 and BDP-15) in an attempt to construct “structure-inherent organelles-targeted” PSs to endow potential organelle-targeting ability. Pyridinyl PSs displayed potent photodynamic efficacy, and monorigidified PSs were very effective. The monorigidified PS 20 with meta-pyridinyl moiety displayed the most potent photoactivity and negligible dark toxicity with a favorable dark/phototoxicity ratio (>4800). To our surprise, monorigidified PS with meta-pyridinyl moiety (e.g., 20) was lipid droplet-targeted. 20 showed good cellular uptake and intracellular ROS generation compared with BDP-15. The preliminary cell death process exploration indicated that 20 resulted in lipid peroxidation and induced cell death through an iron-independent ferroptosis-like cell death pathway. In vivo antitumor efficacy experiments manifested that 20 significantly inhibited tumor growth and outperformed BDP-15 and Ce6 even under a single low-dose light irradiation (30 J/cm2).
中文翻译：
吡啶或吡啶取代的Aza-BODIPY光敏剂的合成和光动力活性
本工作基于单碘Aza-BODIPY PS（ BDP-4和BDP-15 ）设计并构建了各种新型吡啶基和吡啶鎓修饰的Aza-BODIPY PS，试图构建“结构固有细胞器靶向”PS赋予潜在的细胞器靶向能力。吡啶基 PS 显示出强大的光动力功效，并且单刚性化 PS 非常有效。具有间吡啶基部分的单刚性化 PS 20显示出最有效的光活性和可忽略不计的暗毒性，并具有良好的暗/光毒性比 (>4800)。令我们惊讶的是，具有间吡啶基部分（例如20 ）的单刚性化PS是脂滴靶向的。与BDP-15相比， 20显示出良好的细胞摄取和细胞内ROS生成。初步的细胞死亡过程探索表明， 20导致脂质过氧化，并通过铁依赖性铁死亡样细胞死亡途径诱导细胞死亡。体内抗肿瘤功效实验表明，即使在单次低剂量光照射（30 J/cm 2 ）下， 20也能显着抑制肿瘤生长，并且优于BDP-15和Ce6 。
更新日期：2024-08-21
中文翻译：
吡啶或吡啶取代的Aza-BODIPY光敏剂的合成和光动力活性
本工作基于单碘Aza-BODIPY PS（ BDP-4和BDP-15 ）设计并构建了各种新型吡啶基和吡啶鎓修饰的Aza-BODIPY PS，试图构建“结构固有细胞器靶向”PS赋予潜在的细胞器靶向能力。吡啶基 PS 显示出强大的光动力功效，并且单刚性化 PS 非常有效。具有间吡啶基部分的单刚性化 PS 20显示出最有效的光活性和可忽略不计的暗毒性，并具有良好的暗/光毒性比 (>4800)。令我们惊讶的是，具有间吡啶基部分（例如20 ）的单刚性化PS是脂滴靶向的。与BDP-15相比， 20显示出良好的细胞摄取和细胞内ROS生成。初步的细胞死亡过程探索表明， 20导致脂质过氧化，并通过铁依赖性铁死亡样细胞死亡途径诱导细胞死亡。体内抗肿瘤功效实验表明，即使在单次低剂量光照射（30 J/cm 2 ）下， 20也能显着抑制肿瘤生长，并且优于BDP-15和Ce6 。
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