Aminopyrazole‐substituted metallophthalocyanines: Preparation, aggregation behavior, and investigation of metabolic enzymes inhibition properties

Abstract

The synthesis, characterization, aggregation behavior, theoretical studies, and investigation of antimicrobial, antidiabetic, and anticholinergic properties of 4-(2-(5amino-4-(4-bromophenyl)-3-methyl-1H-pyrazol-1-yl)ethoxy)phthalonitrile (2) and its soluble aminopyrazole-substituted peripheral metallo (Mn, Co, and Ni)-phthalocyanine complexes (3-5) are reported for the first time. The synthesized compounds and phthalocyanine complexes were characterized spectroscopically. The new phthalonitrile derivative (2) and its peripheral metallophthalocyanine complexes (3-5) were found to be effective inhibitors of α-glycosidase, acetylcholinesterase (AChE), human carbonic anhydrase I and II isoforms (hCA I and II), and butyrylcholinesterase (BChE) with K i values in the range of 1.55 ± 0.47 to 10.85 ± 3.43 nM for α-glycosidase,8.44 ± 0.32 to 21.31 ± 7.91 nM for hCA I, 11.73 ± 2.82 to 31.03 ± 4.81 nM for hCA II, 101.62 ± 26.58 to 326.54 ± 89.67 nM for AChE, and 68.68 ± 11.15 to 109.53 ± 19.55 nM for BChE. This is the first study of peripherally substituted phthalocyanines containing an aminopyrazole group as potential carbonic anhydrase enzyme inhibitor. Also, the antimicrobial activities of the synthesized compounds were evaluated against six microorganisms (four bacteria and two Candida species) using the broth microdilution method. The gram-positive bacteria were detected to be more sensitive than gram-negative bacteria and yeasts in the synthesized compounds. K E Y W O R D S acetylcholinesterase, anticholinergic, antidiabetic, antimicrobial, aminopyrazole, carbonic anhydrase, phthalocyanine

Concise syntheses and some biological activities of dl‐2,5‐di‐O‐methyl‐chiro‐inositol, dl‐1,4‐di‐O‐methyl‐scyllo‐inositol, and dl‐1,6‐dibromo‐1,6‐dideoxy‐2,5‐di‐O‐methyl‐chiro‐inositol

“…As AD is recognized with acetylcholine (ACh) deficit in the brain of patients with AD, AChE inhibitors have become the most prescribed medication class in the curation of AD. [ 62, 63 ] Indeed, it is recorded that AD is related to metal agglomeration in senile plaques formed in oxidative stress and patients. Then, it is fundamental that any potential medication that can be used for the duration of AD has both cholinesterases inhibitory as well as antioxidant effects.…”

“…The AD pathogenesis is not fully clarified; therefore, there is no therapy for the disease, except for symptomatic curation against mild-to-moderate AD kinds. As AD is recognized with acetylcholine (ACh) deficit in the brain of patients with AD, AChE inhibitors have become the most prescribed medication class in the curation of AD [62,63]. Indeed, it is recorded that AD is related to metal agglomeration in senile plaques formed in oxidative stress and patients.…”

In vitro inhibitory effects of some acetophenone derivatives on some metabolic enzymes and molecular docking

“…From these graphs, half-maximal inhibitor concentrations (IC 50 ) of acetophenone derivatives 1-6 were determined. [47,48] Also, for K i values, three different concentrations of acetophenone derivatives 1-6 were used in this paper. Then, Lineweaver-Burk graphs were drawn according to these measurements.…”

The inhibition profile of sesamol against α-glycosidase and acetylcholinesterase enzymes

“…[57] Measurement of α-glycosidase inhibitory activity For determination of α-glycosidase activity, p-NPG was used as the substrate. [58] For this purpose, sesamol was prepared by dissolving ethanol (1 mg mL −1 ). Firstly, 0.2 mL of NaH 2 PO 4 with pH 7.4 and 20 μL of enzyme solution were mixed.…”