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 Ki values were recorded between 11.17 ± 1.03 and 83.28 ± 11.08 μM. Against the BChE, the compounds demonstrated Ki values from 7.55 ± 0.98 to 81.35 ± 12.80 μM. Also, these compounds (1–7) effectively inhibited α‐glycosidase, with Ki values in the range of 744.87 ± 67.33 to 1094.38 ± 88.91 μM. For α‐glycosidase, the most effective Ki values of phthalocyanines 3 and 6 were with Ki 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‐ylmethoxysubstituted phthalocyanines can be considered as potential agents for the treatment of Alzheimer's diseases and diabetes mellitus.