Potential water-soluble metal phthalocyanine candidates for the treatment of Alzheimer's disease: Synthesis, cholinesterase enzyme inhibition, kinetic analysis and cytotoxicity against human neuroblastoma (SH-SY5Y)

Abstract

In this study, manganese (III), cobalt (II), copper (II) and zinc (II) phthalocyanines and their quaternized cationic derivatives bearing morpholine groups in the non-peripheral position were producedand characterized by various spectroscopic techniques such as UV-Vis, FT-IR, 1H and 13C NMR (only for Zn(II)), MALDI-TOF mass spectra. The inhibitory potential of new compounds on AChE and BuChE enzymes was investigated and IC50 values were determined. It was found that water-soluble derivatives showed stronger inhibitory properties. The most effective compounds in AChE inhibition were water-soluble zinc (II) phthalocyanine (ZT6Q) (IC50 = 0.85 +/- 0.18 mu M) and water-soluble manganese (III) phthalocyanine ZT3Q (IC50 = 2.26 +/- 0.38 mu M), while ZT6Q showed the strongest effect in BuChE inhibition (IC50 = 5.15 +/- 0.48 mu M). Lineweaver-Burk analyses revealed that these compounds inhibited both enzymes in a mixed manner. Ki and Kii values were also calculated. In cell viability tests against human neuroblastoma (SH-SY5Y), ZT6Q did not show cytotoxic effects up to 10 mu M, on the contrary, they increased cell viability. However, ZT3Q exhibited higher cytotoxicity at 48 h exposure. The findings indicate that these compounds can be evaluated as potential therapeutic agents.