Synthesis and Photodynamic Activities of Pyridine- or Pyridinium-Substituted Aza-BODIPY Photosensitizers.
Chang LiuChuan LiuXin JiWeili ZhaoXiaochun DongPublished in: Journal of medicinal chemistry (2024)
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/cm 2 ).
Keyphrases
- cell death
- cancer therapy
- low dose
- fluorescent probe
- cell cycle arrest
- living cells
- drug delivery
- fatty acid
- photodynamic therapy
- high dose
- oxidative stress
- anti inflammatory
- high throughput
- wastewater treatment
- radiation therapy
- reactive oxygen species
- drug induced
- radiation induced
- risk assessment
- molecular docking
- molecular dynamics simulations
- endothelial cells