Synthesis, In Vitro Evaluation and Molecular Docking of the 5-Acetyl-2-aryl-6-hydroxybenzo[ b]furans against Multiple Targets Linked to Type 2 Diabetes

Malose J Mphahlele; Yee Siew Choong; Marole M Maluleka; Samantha Gildenhuys

doi:10.3390/biom10030418

Synthesis, In Vitro Evaluation and Molecular Docking of the 5-Acetyl-2-aryl-6-hydroxybenzo[ b]furans against Multiple Targets Linked to Type 2 Diabetes

Biomolecules. 2020 Mar 7;10(3):418. doi: 10.3390/biom10030418.

Authors

Malose J Mphahlele¹, Yee Siew Choong², Marole M Maluleka¹, Samantha Gildenhuys³

Affiliations

¹ Department of Chemistry, University of South Africa, Private Bag X06, Florida 1710, South Africa.
² Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Penang 11800, Malaysia.
³ Department of Life & Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Private Bag X06, Florida 1710, South Africa.

Abstract

The 5-acetyl-2-aryl-6-hydroxybenzo[b]furans 2a-h have been evaluated through in vitro enzymatic assay against targets which are linked to type 2 diabetes (T2D), namely, α-glucosidase, protein tyrosine phosphatase 1B (PTP1B) and β-secretase. These compounds have also been evaluated for antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging method. The most active compounds against α-glucosidase and/or PTP1B, namely, 4-fluorophenyl 2c, 4-methoxyphenyl 2g and 3,5-dimethoxyphenyl substituted 2h derivatives were also evaluated for potential anti-inflammatory properties against cyclooxygenase-2 activity. The Lineweaver-Burk and Dixon plots were used to determine the type of inhibition on compounds 2c and 2h against α-glucosidase and PTP1B receptors. The interactions were investigated in modelled complexes against α-glucosidase and PTP1B via molecular docking.

Keywords: 5-acetyl-2-aryl-6-hydroxybenzo[b]furans; antioxidant activity; cyclooxygenase-2; molecular docking; protein tyrosine phosphatase 1B; α-glucosidase; β-secretase.

Publication types

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

MeSH terms

Amyloid Precursor Protein Secretases* / antagonists & inhibitors
Amyloid Precursor Protein Secretases* / chemistry
Cyclooxygenase 2 / chemistry
Diabetes Mellitus, Type 2 / drug therapy
Diabetes Mellitus, Type 2 / enzymology*
Furans / chemical synthesis
Furans / chemistry*
Glycoside Hydrolase Inhibitors / chemistry*
Humans
Hypoglycemic Agents / chemistry*
Molecular Docking Simulation*
Protein Tyrosine Phosphatase, Non-Receptor Type 1* / antagonists & inhibitors
Protein Tyrosine Phosphatase, Non-Receptor Type 1* / chemistry
alpha-Glucosidases / chemistry*

Substances

Furans
Glycoside Hydrolase Inhibitors
Hypoglycemic Agents
Cyclooxygenase 2
PTGS2 protein, human
PTPN1 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 1
alpha-Glucosidases
Amyloid Precursor Protein Secretases