Insight into the PTP1B Inhibitory Activity of Arylbenzofurans: An In Vitro and In Silico Study
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 regardin...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-08-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/24/16/2893 |
| _version_ | 1819161469487415296 |
|---|---|
| author | Srijan Shrestha Su Hui Seong Seul Gi Park Byung Sun Min Hyun Ah Jung Jae Sue Choi |
| author_facet | Srijan Shrestha Su Hui Seong Seul Gi Park Byung Sun Min Hyun Ah Jung Jae Sue Choi |
| author_sort | Srijan Shrestha |
| collection | DOAJ |
| description | 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 <i>Morus alba.</i> All compounds demonstrated potent inhibitory activity with IC<sub>50</sub> values ranging from 3.11 to 53.47 µM. Among the tested compounds, MD2 showed the strongest activity (IC<sub>50</sub>, 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. |
| first_indexed | 2024-12-22T17:12:50Z |
| format | Article |
| id | doaj.art-8c71c9459ecf40738216eee0a8c605ad |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-22T17:12:50Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-8c71c9459ecf40738216eee0a8c605ad2022-12-21T18:19:00ZengMDPI AGMolecules1420-30492019-08-012416289310.3390/molecules24162893molecules24162893Insight into the PTP1B Inhibitory Activity of Arylbenzofurans: An In Vitro and In Silico StudySrijan Shrestha0Su Hui Seong1Seul Gi Park2Byung Sun Min3Hyun Ah Jung4Jae Sue Choi5Department of Food and Life Science, Pukyong National University, Busan 48513, KoreaDepartment of Food and Life Science, Pukyong National University, Busan 48513, KoreaDepartment of Food Science and Human Nutrition, Chonbuk National University, Jeonju 54896, KoreaCollege of Pharmacy, Drug Research and Development Center, Catholic University of Daegu, Gyeongbuk 38430, KoreaDepartment of Food Science and Human Nutrition, Chonbuk National University, Jeonju 54896, KoreaDepartment of Food and Life Science, Pukyong National University, Busan 48513, KoreaProtein 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 <i>Morus alba.</i> All compounds demonstrated potent inhibitory activity with IC<sub>50</sub> values ranging from 3.11 to 53.47 µM. Among the tested compounds, MD2 showed the strongest activity (IC<sub>50</sub>, 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.https://www.mdpi.com/1420-3049/24/16/28932-arylbenzofuransPTP1BT2DMin silico studies |
| spellingShingle | Srijan Shrestha Su Hui Seong Seul Gi Park Byung Sun Min Hyun Ah Jung Jae Sue Choi Insight into the PTP1B Inhibitory Activity of Arylbenzofurans: An In Vitro and In Silico Study Molecules 2-arylbenzofurans PTP1B T2DM in silico studies |
| title | Insight into the PTP1B Inhibitory Activity of Arylbenzofurans: An In Vitro and In Silico Study |
| title_full | Insight into the PTP1B Inhibitory Activity of Arylbenzofurans: An In Vitro and In Silico Study |
| title_fullStr | Insight into the PTP1B Inhibitory Activity of Arylbenzofurans: An In Vitro and In Silico Study |
| title_full_unstemmed | Insight into the PTP1B Inhibitory Activity of Arylbenzofurans: An In Vitro and In Silico Study |
| title_short | Insight into the PTP1B Inhibitory Activity of Arylbenzofurans: An In Vitro and In Silico Study |
| title_sort | insight into the ptp1b inhibitory activity of arylbenzofurans an in vitro and in silico study |
| topic | 2-arylbenzofurans PTP1B T2DM in silico studies |
| url | https://www.mdpi.com/1420-3049/24/16/2893 |
| work_keys_str_mv | AT srijanshrestha insightintotheptp1binhibitoryactivityofarylbenzofuransaninvitroandinsilicostudy AT suhuiseong insightintotheptp1binhibitoryactivityofarylbenzofuransaninvitroandinsilicostudy AT seulgipark insightintotheptp1binhibitoryactivityofarylbenzofuransaninvitroandinsilicostudy AT byungsunmin insightintotheptp1binhibitoryactivityofarylbenzofuransaninvitroandinsilicostudy AT hyunahjung insightintotheptp1binhibitoryactivityofarylbenzofuransaninvitroandinsilicostudy AT jaesuechoi insightintotheptp1binhibitoryactivityofarylbenzofuransaninvitroandinsilicostudy |