Tetra-2,3-pyrazinoporphyrazines with externally appended pyridine rings. 17. Photosensitizing properties and cellular effects of ZnII octacationic and ZnII/PtII hexacationic macrocycles in aqueous media: Perspectives of multimodal anticancer potentialities

The photosensitizing activity of two multiply charged porphyrazine derivatives, i.e. the ZnII species [(CH3)8LZn]8+ and the ZnII/PtII heterobimetallic complex [(PtCl2)(CH3)6LZn]6+ (neutralized byI- ions; L = tetrakis-2,3-[5,6-di(2-pyridyl)pyrazino]porphyrazinato dianion) has been examined in the water medium in the presence of SDS under experimental conditions in which the two species are present exclusively in their monomeric form. The determined quantum yield values (ΦΔ) for both complexes, of interest in photodynamic therapy (PDT), are 2.3–2.5 higher than that of the aluminium compound PcAlSmix (Photosens®) used as the reference standard, an encouraging result for the application of the two cationic species as anticancer curative drugs in PDT. Investigation was also extended to explore the cellular effects on the melanoma C8161 and the oral squamous carcinoma CA-1 cell lines like viability, cellular uptake, cell death modality and cell cycle distribution experiments. The IC50 values for the ZnII and ZnII/PtII cations are consistently lower than those of the reference standard, thus the degree of efficiency as anticancer agents being in the order octacation ≫ hexacation > PcAlSmix. A large prevalence of apoptosis with respect to necrosis is observed for both charged complexes. Thus, all achieved information from photoactivity and in vitro tests in water solution further enhance perspectives for the application of the two ZnII cation [(CH3)8LZn]8+ and the related ZnII/PtII analog [(PtCl2)(CH3)6LZn]6+ as potential bi-multimodal anticancer drugs. © 2017