Novel BODIPY Dyes with a Meso-Benzoxadiazole Substituent: Synthesis, Photophysical Studies, and Cytotoxic Activity...

Background/Objectives: Novel boron dipyrromethene derivatives with a heterocyclic, benzoxadiazole substituent were obtained as potential candidates for the photodynamic therapy (PDT) of cancers. Photochemical properties (e.g., singlet oxygen generation quantum yields (Φ_Δ), absorption, and emission spectra) and cytotoxic activity studies in normoxic and hypoxic conditions were performed to verify the potential of novel BODIPYs as photosensitizers for PDT. Methods: Obtained dyes were characterized using mass spectrometry and various NMR techniques. The relative method with Rose Bengal as a reference and 1,3-diphenylisobenzofuran as a singlet oxygen quencher was used to determine Φ_Δ values. The in vitro studies were conducted on human ovarian carcinoma (A2780) and human breast adenocarcinoma (MDA-MB-231) cells. Results: Photochemical studies showed that the presence of benzoxadiazole moiety only slightly affected the localization of the absorption maxima but resulted in fluorescence quenching compared with meso-phenyl-substituted analogs. In addition, brominated and iodinated analogs revealed a high ability to generate singlet oxygen. Anticancer studies showed high light-induced cytotoxicity of BODIPYs containing heavy atoms with very low IC₅₀ values in the 3.5-10.3 nM range. Further experiments revealed that both compounds also demonstrated phototoxic activity under hypoxic conditions. The most potent cytotoxic effect in these conditions was observed in the iodinated BODIPY analog with IC₅₀ values of about 0.3 and 0.4 μM for A2780 and MDA-MB-231 cells, respectively. Conclusions: The results of this study highlighted the advantages and some potential drawbacks of BODIPY compounds with heavy atoms and benzoxadiazole moiety as a useful scaffold in medicinal chemistry for designing new photosensitizers.