Synthesis and characterization of new thionine derivative for application in photodynamic therapy

M.S. GUALDESI ; J. VARA ; L. PEREYRA; C.I. ALVAREZ IGARZABAL ; C.S. ORTIZ

Cordoba

Otro; RICIFA 2020+1; 2021

UNITEFA

Photodynamic therapy (PDT) has become a well-studied therapy for oncological and non-oncological diseases. However, the rational design of novel photosensitizers (PS) with desirable features remains a big challenge for the pharmaceutical industry. To optimize the properties of the photosensitizers currently used, a new derivative of thionine was synthesized and characterized. The effect of bromination reactions on the physicochemical properties of the PS, such as chemical ionization constant (pKa), chemical and photochemical stability, aggregation, and quantum yield of 1O2 production, was also evaluated. Dibrominated thionine (ThBr2) was obtained by electrophilic aromatic substitution, and it was unequivocally characterized by NMR and other spectroscopic techniques. This novel compound showed high chemical and photochemical stability. It was also observed that bromination decreased the ionization constant and increased the aggregation of this photosensitizer in an aqueous medium. For this reason, the new compound showed a lower quantum yield of singlet oxygen production, despite the heavy atom effect that was expected. Nevertheless, when photohemolysis assays were run, the dibrominated thionine exhibited greater cell damage after photodynamic treatment. In conclusion, ThBr2 is a good candidate for PDT, although it is necessary to develop a vehiculization system to avoid aggregation and enhance its efficiency.