Screening of Carbonic Anhydrase, Acetylcholinesterase, Butyrylcholinesterase, and α-Glycosidase Enzyme Inhibition Effects and Antioxidant Activity of Coumestrol

Molecules. 2022 May 11;27(10):3091. doi: 10.3390/molecules27103091.

Abstract

Coumestrol (3,9-dihydroxy-6-benzofuran [3,2-c] chromenone) as a phytoestrogen and polyphenolic compound is a member of the Coumestans family and is quite common in plants. In this study, antiglaucoma, antidiabetic, anticholinergic, and antioxidant effects of Coumestrol were evaluated and compared with standards. To determine the antioxidant activity of coumestrol, several methods-namely N,N-dimethyl-p-phenylenediamine dihydrochloride radical (DMPD•+)-scavenging activity, 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonate) radical (ABTS•+)-scavenging activity, 1,1-diphenyl-2-picrylhydrazyl radical (DPPH)-scavenging activity, potassium ferric cyanide reduction ability, and cupric ion (Cu2+)-reducing activity-were performed. Butylated hydroxyanisole (BHA), Trolox, α-Tocopherol, and butylated hydroxytoluene (BHT) were used as the reference antioxidants for comparison. Coumestrol scavenged the DPPH radical with an IC50 value of 25.95 μg/mL (r2: 0.9005) while BHA, BHT, Trolox, and α-Tocopherol demonstrated IC50 values of 10.10, 25.95, 7.059, and 11.31 μg/mL, respectively. When these results evaluated, Coumestrol had similar DPPH-scavenging effect to BHT and lower better than Trolox, BHA and α-tocopherol. In addition, the inhibition effects of Coumestrol were tested against the metabolic enzymes acetylcholinesterase (AChE), butyrylcholinesterase (BChE), carbonic anhydrase II (CA II), and α-glycosidase, which are associated with some global diseases such as Alzheimer's disease (AD), glaucoma, and diabetes. Coumestrol exhibited Ki values of 10.25 ± 1.94, 5.99 ± 1.79, 25.41 ± 1.10, and 30.56 ± 3.36 nM towards these enzymes, respectively.

Keywords: acetylcholinesterase; antioxidant activity; butyrylcholinesterase; carbonic anhydrase; coumestrol; phenolic compound; α-glycosidase.

MeSH terms

  • Acetylcholinesterase
  • Antioxidants* / chemistry
  • Antioxidants* / pharmacology
  • Butylated Hydroxyanisole / pharmacology
  • Butylated Hydroxytoluene / pharmacology
  • Butyrylcholinesterase
  • Carbonic Anhydrases*
  • Coumestrol / pharmacology
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology
  • Glycoside Hydrolases
  • alpha-Tocopherol / pharmacology

Substances

  • Antioxidants
  • Free Radical Scavengers
  • Butylated Hydroxytoluene
  • Butylated Hydroxyanisole
  • Acetylcholinesterase
  • Butyrylcholinesterase
  • Glycoside Hydrolases
  • Carbonic Anhydrases
  • alpha-Tocopherol
  • Coumestrol

Grants and funding

İlhami Gulcin is a member of the Turkish Academy of Sciences (TÜBA). He would like to extend his sincere appreciation to the TÜBA for financial support. Saleh Alwasel would like to extend his sincere appreciation to the Researchers Supporting Project (RSP-2022/59), King Saud University, Saudi Arabia.