Pyridinium Alkynylanthracenes as Sensitizers for Photodynamic Therapy. (15th November 2021)

• Record Type: Journal Article
• Authors: Fudickar, Werner; Roder, Phillip; Listek, Martin; Hanack, Katja; Linker, Torsten
• Is Part Of: Photochemistry and photobiology. Volume 98:Number 1(2022)
• Page Start: 193
• Page End: 201
• Publication Date: 2021-11-15
• Subjects: Photochemistry -- Periodicals; Light -- Physiological effect -- Periodicals; 541.35
• DOI: 10.1111/php.13554
• Languages: English
• ISSNs: 0031-8655

Abstract

Abstract: Photodynamic therapy (PDT) is a mild but effective method to treat certain types of cancer upon irradiation with visible light. Here, three isomeric methylpyridinium alkynylanthracenes 1 o─p were evaluated as sensitizers for PDT. Upon irradiation with blue or green light, all three compounds show the ability to initiate strand breaks of plasmid DNA. The mayor species responsible for cleavage is singlet oxygen ( 1 O2 ) as confirmed by scavenging reagents. Only isomers 1 m and 1 p can be incorporated into HeLa cells, whereas isomer 1 o cannot permeate through the membrane. While isomer 1 m targets the cell nucleus, isomer 1 p assembles in the cellular cytoplasm and impacts the cellular integrity. This is in accordance with a moderate toxicity of 1 p in the dark, whereas 1 m exhibits no dark toxicity. Both isomers are suitable as PDT reagents, with a CC50 of 3 μm and 75 nm, for 1 p and 1 m, respectively. Thus, derivative 1 m, which can be easily synthesized, becomes an interesting candidate for cancer therapy. Abstract : Three isomeric cationic pyridinium alkynylanthracenes have been applied as sensitizers for photodynamic therapy. When they were administered to HeLa cancer cells they showed different behavior. While one isomer did not enter the cell and showed no toxicity, one isomer was able to accumulate within the cytoplasm with moderate phototoxicity and low dark toxicity, whereas the last isomer was found in the nucleus with a high toxicity < 100 nm but no dark toxicity. We propose a structure‐activity relationship based on the separation of charges.