Benzofuran-selenadiazole hybrids as novel α-glucosidase and cyclooxygenase-2 inhibitors with antioxidant and cytotoxic properties

Temitope O Olomola; Malose J Mphahlele; Samantha Gildenhuys

doi:10.1016/j.bioorg.2020.103945

Benzofuran-selenadiazole hybrids as novel α-glucosidase and cyclooxygenase-2 inhibitors with antioxidant and cytotoxic properties

Bioorg Chem. 2020 Jul:100:103945. doi: 10.1016/j.bioorg.2020.103945. Epub 2020 May 18.

Authors

Temitope O Olomola¹, Malose J Mphahlele², Samantha Gildenhuys³

Affiliations

¹ Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South Africa.
² Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South Africa. Electronic address: mphahmj@unisa.ac.za.
³ Department of Life & Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Private Bag X06, Florida 1710, South Africa.

PMID: 32450390
DOI: 10.1016/j.bioorg.2020.103945

Abstract

Series of 2-arylbenzofuran-1,2,3-selenodiazole hybrids were prepared via multiple reactions and then evaluated in vitro through enzymatic assay for inhibitory effect against α-glucosidase and cyclooxygenase-2 (COX-2) activities including antioxidant activity. The presence of 1,2,3-selenodiazole moiety resulted in increased inhibitory effect for compounds 4a-f against α-glucosidase and COX-2 activities, and increased free radical scavenging activity. 6-Acetoxy-2-phenyl-5-(1,2,3-selenadiazol-4-yl)benzofuran (4a) and its 2-(4-methoxyphenyl) substituted derivative (4f) were, in turn, screened for antiproliferation against the breast MCF-7 cancer cell line and for cytotoxicity on the human embryonic kidney derived Hek293-T cells. A cell-based antioxidant activity assay involving lipopolysaccharide induced reactive oxygen species production in these cells was performed. Molecular docking has also been performed on these two compounds to predict protein-ligand interactions against α-glucosidase and COX-2.

Keywords: Cyclooxygenase-2, antioxidant activity; Cytotoxicity; Molecular docking; Selenadiazol-4-yl-benzofurans; α-glucosidase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antioxidants / chemistry*
Azoles / chemistry*
Benzofurans / chemistry*
Binding Sites
Catalytic Domain
Cell Line
Cell Survival / drug effects
Cyclooxygenase 2 / chemistry*
Cyclooxygenase 2 / metabolism
Cyclooxygenase 2 Inhibitors / chemistry*
Cyclooxygenase 2 Inhibitors / metabolism
Cyclooxygenase 2 Inhibitors / pharmacology
Glycoside Hydrolase Inhibitors / chemistry*
Glycoside Hydrolase Inhibitors / metabolism
Glycoside Hydrolase Inhibitors / pharmacology
Humans
Kinetics
Lipopolysaccharides / pharmacology
MCF-7 Cells
Molecular Conformation
Molecular Docking Simulation
Reactive Oxygen Species / metabolism
Structure-Activity Relationship
alpha-Glucosidases / chemistry*
alpha-Glucosidases / metabolism

Substances

Antioxidants
Azoles
Benzofurans
Cyclooxygenase 2 Inhibitors
Glycoside Hydrolase Inhibitors
Lipopolysaccharides
Reactive Oxygen Species
Cyclooxygenase 2
alpha-Glucosidases
benzofuran