2. Academic Validation
  3. Insight into the PTP1B Inhibitory Activity of Arylbenzofurans: An In Vitro and In Silico Study

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

  • Molecules. 2019 Aug 9;24(16):2893. doi: 10.3390/molecules24162893.
Srijan Shrestha 1 2,  Su Hui Seong 1,  Seul Gi Park 3,  Byung Sun Min 4,  Hyun Ah Jung 5,  Jae Sue Choi 6
Affiliations

Affiliations

  • 1 Department of Food and Life Science, Pukyong National University, Busan 48513, Korea.
  • 2 Discipline of Pharmacology, School of Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide 5005, South Australia, Australia.
  • 3 Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju 54896, Korea.
  • 4 College of Pharmacy, Drug Research and Development Center, Catholic University of Daegu, Gyeongbuk 38430, Korea.
  • 5 Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju 54896, Korea. [email protected].
  • 6 Department of Food and Life Science, Pukyong National University, Busan 48513, Korea. [email protected].
PMID: 31395821 DOI: 10.3390/molecules24162893
Abstract

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 Morus alba. All compounds demonstrated potent inhibitory activity with IC50 values ranging from 3.11 to 53.47 µM. Among the tested compounds, MD2 showed the strongest activity (IC50, 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.

Keywords

2-arylbenzofurans; PTP1B; T2DM; in silico studies.

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