Synthesis, characterization and investigation of cholinesterase inhibitory properties of novel peripherally tetra substituted metal-free and metallo-phthalocyanines

In this study, the phthalonitrile compound (3) and peripherally tetra substituted metal-free (4), lead(II) (5), nickel (II) (6) and cobalt(II) (7) phthalocyanines were synthesized for the first time. The characterization of the novel complexes was performed with FT-IR, H-1 NMR, C-13 NMR, UV-Vis and mass spectroscopy. The aggregation properties of novel phthalocyanine compounds (4-7) were investigated by using visible spectroscopy in grade DMSO-PBS mixtures. The acetylcholinesterase/butyrylcholinesterase (AChE/BuChE) inhibitory effects of compounds were investigated to determine the therapeutic potential of compounds in the treatment of neurodegenerative diseases. Among tested compounds, (6) had the most promising agent against AChE with IC50 value of 65.04 +/- 0.82 mu M while (5) showed the strongest BuChE inhibitory effects with IC50 value of 46.23 +/- 0.78 mu M. The kinetic analysis demonstrated that (5) and (6) were competitive inhibitors against cholinesterase enzymes. The K-i values of compounds were estimated 28.23 +/- 0.30 and 31.04 +/- 0.50 mu M against AChE, 16.13 +/- 0.44 and 94.20 +/- 1.40 mu M against BuChE. Our results claim that (5) might be effective to prevent AD thanks to its anti-cholinesterase effects and low aggregation properties. (C) 2019 Elsevier B.V. All rights reserved.