LAUSR

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.