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-ylmethoxysubstituted phthalocyanines can be considered as potential agents for the treatment of Alzheimer's diseases and diabetes mellitus.

Synthesis and biological evaluation of peripherally tetra‐({6‐[3‐(dimethylamino)phenoxy]hexyl}oxy) substituted water‐soluble phthalocyanines as cholinesterases inhibitors

“…[ 43 ] Another study, Güzel et al reported furan‐2‐ylmethoxy‐substituted copper and manganese Pcs on cholinesterases inhibited AChE with 15.91 and 48.04 μM, respectively. [ 32 ] These results showed that our compounds had higher inhibitory effects than non‐peripherally (4‐isopropylbenzyl)oxy‐substituted and furan‐2‐ylmethoxy‐substituted Pcs compounds.…”

“…[27,28] Recently, there have been many studies on the pharmacological and biological activities of Pcs in the literature, especially cholinesterase inhibitory effects. [29][30][31][32][33][34][35] Günsel et al reported that non-peripheral 2-mercaptoethanesulfonate substituted metal-free, zinc, and gallium Pcs inhibited AChE and BuChE. [29] Arslan et al investigated in vitro cholinesterases inhibitory effects of 1,2,3-triazole substituted metal-free, zinc, cobalt Pcs, and their water-soluble derivatives.…”

A review on α-glucosidase inhibitory activity of first row transition metal complexes: a futuristic strategy for treatment of type 2 diabetes

“…Complex 138 having oxy methyl furan group (L60, Table 7 , entry 1) had the worst inhibitory activity (IC 50 = 902.83 μM) comparing with acarbose (IC 50 = 0.38 μM). 106 Moreover, complexes 139 (IC 50 = 7.08 μM, acarbose = 63.03 μM), 107 141 (IC 50 = 22.21 μM, acarbose = 51.45 μM), 108 and 144 (IC 50 = 2.44 μM, acarbose = 22.80 μM), 110 displayed good inhibitory activity. However, it indicated the efficacy of involved ligands in the order of L62 > L64 > L72.…”

Self-Healing Systems in Silicon Anodes for Li-Ion Batteries

“…There are several systems used to impart self-healing ability to materials ( Figure 1 ). These systems can be classified into two main groups: capsule-based healing (bead, fiber, and/or vascular type and mechanochemical), which is autonomous, and healing by the action of nonautonomous external stimuli [ 1 , 8 , 9 , 10 , 11 , 12 , 13 ].…”