2-Naphthol Moiety of Neocarzinostatin Chromophore as a Novel Protein-Photodegrading Agent and Its Application as a H₂O₂-Activatable Photosensitizer

A 2-naphthol derivative 2 corresponding to the aromatic ring moiety of neocarzinostatin chromophore was found to degrade proteins under photo-irradiation with long-wavelength UV light without any additives under neutral conditions. Structure–activity relationship studies of the derivative revealed that methylation of the hydroxyl group at the C2 position of 2 significantly suppressed its photodegradation ability. Furthermore, a purpose-designed synthetic tumor-related biomarker, a H₂O₂-activatable photosensitizer 8 possessing a H₂O₂-responsive arylboronic ester moiety conjugated to the hydroxyl group at the C2 position of 2, showed significantly lower photodegradation ability compared to 2. However, release of the 2 from 8 by reaction with H₂O₂ regenerated the photodegradation ability. Compound 8 exhibited selective photo-cytotoxicity against high H₂O₂-expressing cancer cells upon irradiation with long-wavelength UV light.