Photostable Platinated Bacteriochlorins as Potent Photodynamic Agents.

Ngoc An Le, Vipin Babu, Martina Kalt, Lukas Schneider, Frank Schumer, Bernhard Spingler

Journal of medicinal chemistry 2021 May 27

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Photodynamic therapy (PDT) is used to treat various cancerous diseases. Recently, we have demonstrated that platinated pyridyl-substituted porphyrins are potent agents for PDT with very high phototoxicity (IC50 down to 17 nM) and excellent phototoxic indices of higher than 5800 (p.i. = IC50(dark)/IC50(light)) [Rubbiani, R. et al., Chem. Commun. 2020, 56, 14373]. However, the absorption of porphyrins is not ideal for the treatment of larger tumors because they essentially do not absorb light between 650 and 850 nm. Herein, we report stable conjugates of a novel bacteriochlorin with cisplatin and transplatin. They exhibit extremely high phototoxicity (IC50 values down to 6 nM, irradiated with a 750 nm LED at a fluence of 5 J/cm2), very low dark toxicity, and thereby extremely high phototoxic indices up to 8300. Based on these exciting results, we believe that platinated bacteriochlorins are promising candidates for further investigation as novel PDT anticancer agents.

Citation

Ngoc An Le, Vipin Babu, Martina Kalt, Lukas Schneider, Frank Schumer, Bernhard Spingler. Photostable Platinated Bacteriochlorins as Potent Photodynamic Agents. Journal of medicinal chemistry. 2021 May 27;64(10):6792-6801