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

BIYIKLIOĞLU Z., Bas H., AKKAYA D., BARUT B.

APPLIED ORGANOMETALLIC CHEMISTRY, vol.36, no.4, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 36 Issue: 4
  • Publication Date: 2022
  • Doi Number: 10.1002/aoc.6580
  • Journal Name: APPLIED ORGANOMETALLIC CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, BIOSIS, Chimica, Communication Abstracts, Compendex, Metadex, DIALNET, Civil Engineering Abstracts
  • Keywords: cholinesterases, kinetic parameter, mixed inhibitor, phthalocyanine, synthesis, ALZHEIMERS-DISEASE, METAL-FREE, AGGREGATION, ELECTROCHEMISTRY, DERIVATIVES, ANTIOXIDANT
  • Karadeniz Technical University Affiliated: Yes

Abstract

In this paper, we synthesized peripherally tetra-({6-[3-(dimethylamino)phenoxy]hexyl}oxy) substituted water-soluble metallophthalocyanines (DM-C6-CoQ, DM-C6-CuQ, DM-C6-MnQ) and investigated their in vitro cholinesterases inhibitory properties by using the spectrophotometric method. The results revealed that the compounds inhibited cholinesterases and had remarkable inhibitory effects when compared with galantamine (p < 0.0001). The IC50 values of the compounds ranged from 2.11 +/- 0.20 to 16.40 +/- 1.25 mu M for AChE and BuChE. Also, the inhibitory type and inhibition constant (K-i) of the compounds were evaluated using Lineweaver-Burk and Dixon plots. These plots showed that DM-C6-CoQ, DM-C6-CuQ, and DM-C6-MnQ were mixed inhibitors against AChE and DM-C6-MnQ is the strongest binding inhibitor to the enzyme. Also, DM-C6-CoQ inhibited BuChE via competitive manner with 10.05 +/- 0.55 mu M of K-i value. These results demonstrated that the compounds might be effective agents against Alzheimer's disease.