Design, synthesis, characterization of peripherally tetra-pyridine-triazole-substituted phthalocyanines and their inhibitory effects on cholinesterases (AChE/BChE) and carbonic anhydrases (hCA I, II and IX)

Arslan T., CEYLAN M. B., Baş H., BIYIKLIOĞLU Z., Senturk M.

DALTON TRANSACTIONS, vol.49, no.1, pp.203-209, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 49 Issue: 1
  • Publication Date: 2020
  • Doi Number: 10.1039/c9dt03897c
  • Journal Name: DALTON TRANSACTIONS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), Chimica, Communication Abstracts, Compendex, EMBASE, MEDLINE
  • Page Numbers: pp.203-209
  • Karadeniz Technical University Affiliated: Yes

Abstract

In this study, phthalocyanine precursors (5 and 9) and 1,2,3-triazole-substituted metal-free and metallo phthalocyanines (9a-c) were designed and synthesized for the first time and evaluated in vitro for key molecular targets. The structures of the novel compounds were characterized via FT-IR, H-1/C-13 NMR, UV-Vis, and mass spectroscopy. The inhibitory activities of the compounds were tested against human carbonic anhydrase isoforms hCA I, II (cytosolic, ubiquitous isozymes), and IX (transmembrane, cancer-associated isozyme) and cholinesterases (AChE and BChE, which are associated with Alzheimer's disease). Among the three phthalocyanines and starting compounds, 9b showed the most interesting profile as a nanomolar selective inhibitor of hCA I (K-i = 37.2 nM) and 9c showed the most effective inhibitory effect on hCA II, IX, AChE and BChE (K-i = 41.9, 27.4, 5.8 and 45.8 nM, respectively). This study is also the first example of cancer-associated isozyme hCA IX inhibition by phthalocyanines.