Porphyrazines containing styryldiazepine rings and their liposomal formulations: preparation, photochemical properties and photodynamic activity against oral cancer cell lines

Photodynamic therapy (PDT) is a novel, alternative, anticancer treatment, which has also been used to cure cardiovascular, dermatological, and ophthalmic diseases as well as various microbial infections. PDT consists of three factors: compound (photosynthesizer), oxygen, and light. Upon irradiation with light of specific wavelength the photosynthesizer undergoes activation and produces reactive oxygen species such as singlet oxygen. As a consequence, it leads to the death of the treated tissue. Here we present our data to the synthesis of prophyrazines and tribenzoporphyrazines containing styryldiazepine rings. Condensation reactions of known dicyanodiazepins with 3,4,5-trimetoxybenzaldehyde and 1-methyl-2-imidazolecarbaldehyde led to the novel 1,4-diazepine-2,3-dicarbonitriles containing arylvinyl substituents. However, only diazepines with 3,4,5-trimetoxyphenyl groups subjected to macrocyclization reactions gave the desired macrocycles of sufficient stability. Novel macrocyclic compounds were characterized using various spectroscopic methods and extensively investigated in photochemical studies. Moreover, their photodynamic activity was examined in vitro using two human oral squamous cell carcinoma cell lines, HSC-3 cells derived from the tongue and H413 cells from the buccal mucosa. Magnesium tribenzoprophyrazine (Pz1) revealed high activity against cancer cells even at low concentrations and low light dose. Moreover, significantly higher cytotoxicity of Pz1 was observed after its incorporation into negatively charged liposomes