Synthesis and characterization of novel bromophenols: Determination of their anticholinergic, antidiabetic and antioxidant activities

Bioorg Chem. 2019 Jun:87:91-102. doi: 10.1016/j.bioorg.2019.03.010. Epub 2019 Mar 6.

Abstract

In this paper, a series of novel bromophenol derivatives were synthesized and evaluated for their acetylcholinesterase and α-glycosidase enzymes inhibition properties and antioxidant activity. Diarylmethanones were synthesized and their bromination was carried out. During bromination, some compounds gave new bromophenols via regioselective O-demethylation. Demethylation of brominated diarylmethanones was also performed with BBr3 to give novel bromophenols. In addition, we examines the antioxidant capacity of novel bromophenol derivatives using several in vitro bioanalytical methodologies such as 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS⋅+) and 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH) radical scavenging activity, Fe3+ and Cu2+ reducing activities and ferrous (Fe2+) ions chelating activities. Also, novel bromophenols and methoxylated bromophenols derivatives were tested against acetylcholinesterase and α-glycosidase, which associated with some metabolic diseases. The novel bromophenols showed Ki values in range of 8.94 ± 0.73-59.45 ± 14.97 nM against AChE and 4.31 ± 1.93-44.14 ± 2.19 nM against α-glycosidase.

Keywords: Acetylcholinesterase; Antioxidant activity; Bromophenols; Diarylmethanones, enzyme inhibition; α-glycosidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Benzothiazoles / antagonists & inhibitors
  • Biphenyl Compounds / antagonists & inhibitors
  • Cholinergic Antagonists / chemical synthesis
  • Cholinergic Antagonists / chemistry
  • Cholinergic Antagonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Eels
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Glycoside Hydrolases / metabolism
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology*
  • Molecular Structure
  • Picrates / antagonists & inhibitors
  • Polybrominated Biphenyls / chemical synthesis
  • Polybrominated Biphenyls / chemistry
  • Polybrominated Biphenyls / pharmacology*
  • Structure-Activity Relationship
  • Sulfonic Acids / antagonists & inhibitors

Substances

  • Antioxidants
  • Benzothiazoles
  • Biphenyl Compounds
  • Cholinergic Antagonists
  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • Picrates
  • Polybrominated Biphenyls
  • Sulfonic Acids
  • 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid
  • 1,1-diphenyl-2-picrylhydrazyl
  • Acetylcholinesterase
  • Glycoside Hydrolases
  • bromophenophos