Synthesis of new chlorin e6 derivatives bearing galactose moieties on the macrocyclic periphery and their structure–activity relationships

Abstract

Recent studies of photosensitizers have increasingly focused on improving their aqueous solubility, reducing dark toxicity and enhancing photodynamic activity. In our work, we have synthesized and characterized a series of chlorin e₆ derivatives varying in the number of galactose moieties in the molecule and way they are linked to the chlorin macrocycle. We established that the quantity and localization of galactose moieties in the macrocycle affects both dark and photoinduced cytotoxicity. All of the studied derivatives exhibited singlet oxygen quantum yield photogeneration comparable to that of the clinically approved chlorin e₆ dimeglumine (Photoditazine®) with marginal exceeding. Although the incorporation of galactose moieties to the periphery of the chlorin macrocycle led to slightly decreased photostability of resulting derivatives, it did not significantly hinder their photodynamic activity. Moreover, cellular uptake of the obtained derivatives was significantly improved compared to that of Photoditazine®. Collectively, favorable spectral, photochemical, photobiological characteristics, along with improved aqueous solubility, suggest that chlorin e₆ derivatives with peripheral galactose substituents are promising photosensitizers for clinical applications.