Water-soluble metallophthalocyanines bearing 1-naphthoxy-4-sulfonic acid sodium salts: Sono-Photochemical and enzyme inhibition potential with molecular docking analysis

Abstract

In this study, we synthesized a novel ligand, sodium 4-(2,3-dicyanophenoxy)naphthalene-1-sulfonate (1), and its metallophthalocyanine derivatives [Zn(II) (2), Ga(III) (3), In(III) (4)] bearing 1-naphthoxy-4-sulfonic acid sodium salt units. These compounds were evaluated for their singlet oxygen generation via photochemical and sonophotochemical methods, and their inhibitory effects against alpha-glycosidase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes. The Ga(III)-phthalocyanine (3) exhibited the highest AChE and BChE inhibition (Ki: 13.37 and 29.15 mu M, respectively), while the Zn(II)-phthalocyanine (2) showed the most potent alpha-glycosidase inhibition (Ki: 14.61 mu M). Molecular docking studies confirmed strong binding affinities of the complexes to their respective targets, with binding energies up to-13.8 Kcal/mol. The results suggest that these water-soluble phthalocyanines have significant potential for use in photodynamic and sonophotodynamic therapy, as well as dual-action treatment strategies targeting neurodegenerative and metabolic disorders.