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

• Published in: Archiv der Pharmazie (Weinheim) 2019-02, Vol.352 (2), p.e1800292-n/a
• Main Authors: Güzel, Emre, Koçyiğit, Ümit M., Arslan, Barış S., Ataş, Mehmet, Taslimi, Parham, Gökalp, Faik, Nebioğlu, Mehmet, Şişman, İlkay, Gulçin, İlhami
• Format: Article
• Language: English
• Subjects: acetylcholinesterase; aminopyrazole; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; anticholinergic; antidiabetic; Antidiabetics; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; antimicrobial; Antimicrobial agents; Bacteria; carbonic anhydrase; Carbonic Anhydrase Inhibitors - chemical synthesis; Carbonic Anhydrase Inhibitors - chemistry; Carbonic Anhydrase Inhibitors - pharmacology; Cholinergic Antagonists - chemical synthesis; Cholinergic Antagonists - chemistry; Cholinergic Antagonists - pharmacology; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Humans; Hypoglycemic Agents - chemical synthesis; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacology; Indoles - chemical synthesis; Indoles - chemistry; Indoles - pharmacology; Metals - chemistry; phthalocyanine; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Structure-Activity Relationship
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.201800292

The synthesis, characterization, aggregation behavior, theoretical studies, and investigation of antimicrobial, antidiabetic, and anticholinergic properties of 4‐(2‐(5‐amino‐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 Ki 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. 4‐(2‐(5‐Amino‐4‐(4‐bromophenyl)‐3‐methyl‐1H‐pyrazol‐1‐yl)ethoxy)phthalonitrile 2 and its soluble aminopyrazole‐substituted peripheral metallophthalocyanine complexes 3–5 were synthesized and assayed for their aggregation behavior, antimicrobial, antidiabetic, and anticholinergic properties. They were found to be effective inhibitors of α‐glycosidase, acetylcholinesterase, human carbonic anhydrase I and II, and butyrylcholinesterase.