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

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2020-03, Vol.10 (3), p.418
• Main Authors: Mphahlele, Malose J, Choong, Yee Siew, Maluleka, Marole M, Gildenhuys, Samantha
• Format: Article
• Language: English
• Subjects: 5-acetyl-2-aryl-6-hydroxybenzo[b]furans; alpha-Glucosidases - chemistry; Amyloid Precursor Protein Secretases - antagonists & inhibitors; Amyloid Precursor Protein Secretases - chemistry; Anti-inflammatory agents; antioxidant activity; Antioxidants; Carbohydrates; Chromatography; Cyclooxygenase 2 - chemistry; Cyclooxygenase-2; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - enzymology; Enzymes; Furans; Furans - chemical synthesis; Furans - chemistry; Glycoside Hydrolase Inhibitors - chemistry; Humans; Hyperglycemia; Hypoglycemic Agents - chemistry; Inflammation; Insulin resistance; Metabolism; molecular docking; Molecular Docking Simulation; NMR; Nuclear magnetic resonance; Oxidative stress; Phosphatase; Physiological aspects; protein tyrosine phosphatase 1b; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - antagonists & inhibitors; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - chemistry; Protein-tyrosine-phosphatase; Secretase; Small intestine; Type 2 diabetes; α-Glucosidase; β-secretase
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom10030418

The 5-acetyl-2-aryl-6-hydroxybenzo[ ]furans - 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 , 4-methoxyphenyl and 3,5-dimethoxyphenyl substituted 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 and against α-glucosidase and PTP1B receptors. The interactions were investigated in modelled complexes against α-glucosidase and PTP1B via molecular docking.