Synthesis of Novel Cationic Photosensitizers Derived from Chlorin for Application in Photodynamic Therapy of Cancer

Abstract

Background: Chlorins (dihydroporphyrins) are tetrapyrrole-based compounds that are more effective in photodynamic therapy than porphyrins. The instability of the compounds and their oxidation to porphyrin limits the use of these compounds. However, the design and synthesis of new stable chlorin-based cationic photosensitizers with the potential for use in cancer photodynamic therapy can be interesting. Methods: In this research, new tetracationic meso substituted chlorins were designed, synthesized, and characterized. After determining the chemical structure and spectroscopic properties of five new photosensitizers, their phototoxicity on breast cancer cell lines (MCF-7) was investigated under optimized conditions in terms of factors such as photosensitizer concentrations and light intensity. Results: The results of cytotoxicity assayed by the MTT method showed that the synthesized compounds, even up to the concentration of 50 μM had very low toxicity in the absence of light, which indicates their safety under dark conditions. Compounds A1 and A3 with the best physicochemical properties such as solubility, high absorption intensity in the effective range of photodynamic therapy, and the high quantum yield of singlet oxygen, had a good toxic effect (IC50 = 0.5 μM) on the cancer cells (MCF-7) in the presence of laser light. Conclusion: According to the obtained results, compounds A1 and A3 have the potential to continue research on PDT for confirmation and use in treatment.