Biologically active phthalocyanine metal complexes: Preparation, evaluation of α-glycosidase and anticholinesterase enzyme inhibition activities, and molecular docking studies

Abstract

In this study, preparation, as well as investigation of α-glycosidase and cholinesterase (ChE) enzyme inhibition activities of furan-2-ylmethoxy-substituted compounds 1-7, are reported. Peripherally, tetra-substituted copper and manganese phthalocyanines (5 and 6) were synthesized for the first time. The substitution of furan-2-ylmethoxy groups provides remarkable solubility to the complex and redshift of the phthalocyanines Q-band. Besides, the inhibitory effects of these compounds on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glycosidase (α-Gly) enzymes have been investigated. The AChE was inhibited by these compounds (1-7) in low micromolar levels, and K _i values were recorded between 11.17 ± 1.03 and 83.28 ± 11.08 µM. Against the BChE, the compounds demonstrated K _i values from 7.55 ± 0.98 to 81.35 ± 12.80 µM. Also, these compounds (1-7) effectively inhibited α-glycosidase, with K _i values in the range of 744.87 ± 67.33 to 1094.38 ± 88.91 µM. For α-glycosidase, the most effective K _i values of phthalocyanines 3 and 6 were with K _i values of 744.87 ± 67.33 and 880.36 ± 56.77 µM, respectively. Moreover, the studied metal complexes were docked with target proteins PDB ID: 4PQE, 1P0I, and 3WY1. Pharmacokinetic parameters and secondary chemical interactions that play an active role in interaction were predicted with docking simulation results. Overall, furan-2-ylmethoxy-substituted phthalocyanines can be considered as potential agents for the treatment of Alzheimer's diseases and diabetes mellitus.

Keywords: cholinesterases; enzyme inhibition; molecular docking; phthalocyanine; α-glycosidase.