The first pyrido[1,2-a]benzimidazole-fused porphyrazine photosensitizers with submicromolar photodynamic activity against cancer cells.

Novel pyrido[1,2-a]benzimidazole-fused tetrapyrrolic photosensitizers with an intense near-infrared absorption (711-747 nm) in the region of high transparency of biological tissues were prepared. Target photosensitizers demonstrated high ΦΔ values (0.49-0.60) resulted from the ability to form triplet states under irradiation. A test with nitroblue tetrazolium showed that in addition to singlet oxygen, they can generate type I reactive oxygen species such as the superoxide anion radical. Water-soluble quaternized forms of target photosensitizers demonstrated low cytotoxicity in the dark and submicromolar phototoxicity against A549, WI38, HCT116, MCF7, A431 and HeLa cell lines. Their phototoxic action is comparable with that of chlorin e6 - a well-known component of the most effective photosensitizers approved for photodynamic therapy, such as Photolon, Photoditazine - but the obtained compounds significantly less cytotoxic in the dark. Using confocal microscopy, it was shown that photosensitizers containing pyrido[1,2-a]benzimidazole cause rapid photoinduced cell necrosis comparable to the necrosis caused by Photolon.