Insight into the PTP1B Inhibitory Activity of Arylbenzofurans: An In Vitro and In Silico Study

• Published in: Molecules (Basel, Switzerland) Switzerland), 2019-08, Vol.24 (16), p.2893
• Main Authors: Shrestha, Srijan, Seong, Su Hui, Park, Seul Gi, Min, Byung Sun, Jung, Hyun Ah, Choi, Jae Sue
• Format: Article
• Language: English
• Subjects: 2-arylbenzofurans; Analogs; Bark; Benzofurans - chemistry; Benzofurans - isolation & purification; Binding sites; Chemical compounds; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Enzyme Inhibitors - chemistry; Enzyme Inhibitors - isolation & purification; Humans; Hydrocarbons; in silico studies; Insulin; Insulin resistance; Ligands; Molecular docking; Molecular Docking Simulation; Morus - chemistry; Morus alba; Pharmacology; Plant Roots - chemistry; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - antagonists & inhibitors; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - chemistry; Protein-tyrosine-phosphatase; PTP1B; Resorcinol; Signal transduction; T2DM; Therapeutic targets; Tyrosine
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24162893

Protein tyrosine phosphatase 1B (PTP1B) plays a specific role as a negative regulator of insulin signaling pathways and is a validated therapeutic target for Type 2 diabetes. Previously, arylbenzofurans were reported to have inhibitory activity against PTP1B. However, detailed investigation regarding their structure activity relationship (SAR) has not been elucidated. The main aim of this work was to investigate the PTP1B inhibitory activity of 2-arylbenzofuran analogs (sanggenofuran A (SA), mulberrofuran D2 (MD2), mulberrofuran D (MD), morusalfuran B (MB), mulberrofuran H (MH)) isolated from the root bark of All compounds demonstrated potent inhibitory activity with IC values ranging from 3.11 to 53.47 µM. Among the tested compounds, MD2 showed the strongest activity (IC , 3.11 µM), followed by MD and MB, while SA and MH demonstrated the lowest activity. Lineweaver-Burk and Dixon plots were used for the determination of inhibition type whereas ligand and receptor interactions were investigated in modeled complexes via molecular docking. Our study clearly supports 2-arylbenzofuran analogs as a promising class of PTP1B inhibitors and illustrates the key positions responsible for the inhibitory activity, their correlation, the effect of prenyl/geranyl groups, and the influence of resorcinol scaffold, which can be further explored in-depth to develop therapeutic agents against T2DM.