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Inhibition of PTP1B by farnesylated 2-arylbenzofurans isolated from Morus alba root bark: unraveling the mechanism of inhibition based on in vitro and in silico studies
Among the 2-arylbenzofuran derivatives isolated from Morus alba, the farnesylated 2-arylbenzofuran is a rarer constituent. The derivative has been reported to exert anti-obesity effect; however, its inhibitory effect on protein tyrosine phosphatase 1B (PTP1B) has not been investigated. In the previo...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Pharmaceutical Society of Korea
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518952/ https://www.ncbi.nlm.nih.gov/pubmed/32978714 http://dx.doi.org/10.1007/s12272-020-01269-4 |
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author | Ha, Manh Tuan Shrestha, Srijan Tran, Thu Huong Kim, Jeong Ah Woo, Mi Hee Choi, Jae Sue Min, Byung Sun |
author_facet | Ha, Manh Tuan Shrestha, Srijan Tran, Thu Huong Kim, Jeong Ah Woo, Mi Hee Choi, Jae Sue Min, Byung Sun |
author_sort | Ha, Manh Tuan |
collection | PubMed |
description | Among the 2-arylbenzofuran derivatives isolated from Morus alba, the farnesylated 2-arylbenzofuran is a rarer constituent. The derivative has been reported to exert anti-obesity effect; however, its inhibitory effect on protein tyrosine phosphatase 1B (PTP1B) has not been investigated. In the previous study, the presence of the farnesyl group in the structure of 2-arylbenzofurans was found to have positive influences on their pancreatic lipase inhibitory activity. In the present study, we have confirmed the authenticity of the notation based on the PTP1B inhibitory activity of farnesylated 2-arylbenzofurans. Specifically, two farnesylated 2-arylbenzofurans [morusalfurans B (2) and C (3)] showed strong inhibitory effects on PTP1B with IC(50) values of 8.92 and 7.26 µM, respectively, which was significantly higher than that of the positive controls [sodium orthovanadate (IC(50) = 15.10 µM) and ursolic acid (IC(50) = 11.34 µM)]. Besides, two 2-arylbenzofurans [morusalfurans A (1) and F (6)], one flavonoid [morusalnol B (9)], and one geranylated stilbene [morusibene A (11)] exhibited PTP1B inhibition with IC(50) values ranging from 11.02 to 26.56 µM. Kinetic studies revealed compounds 2, 3, 6, and 11 as mixed type PTP1B inhibitors, while 1 and 9 are known as noncompetitive. Molecular docking simulations demonstrated that these active compounds can bind with the respective catalytic or/and allosteric sites of PTP1B with negative binding energies and the results are in accordance with that of the kinetic studies. To the best of our knowledge, this is the first time, the PTP1B inhibitory activity of eleven compounds (1–11), as well as the mechanism of action underlying the effects on PTP1B enzyme of the active compounds, were investigated. In vitro and in silico results suggest that the farnesylated 2-arylbenzofurans from M. alba may potentially be utilized as an effective treatment therapy for type 2 diabetes mellitus and its associated complications. |
format | Online Article Text |
id | pubmed-7518952 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Pharmaceutical Society of Korea |
record_format | MEDLINE/PubMed |
spelling | pubmed-75189522020-09-28 Inhibition of PTP1B by farnesylated 2-arylbenzofurans isolated from Morus alba root bark: unraveling the mechanism of inhibition based on in vitro and in silico studies Ha, Manh Tuan Shrestha, Srijan Tran, Thu Huong Kim, Jeong Ah Woo, Mi Hee Choi, Jae Sue Min, Byung Sun Arch Pharm Res Research Article Among the 2-arylbenzofuran derivatives isolated from Morus alba, the farnesylated 2-arylbenzofuran is a rarer constituent. The derivative has been reported to exert anti-obesity effect; however, its inhibitory effect on protein tyrosine phosphatase 1B (PTP1B) has not been investigated. In the previous study, the presence of the farnesyl group in the structure of 2-arylbenzofurans was found to have positive influences on their pancreatic lipase inhibitory activity. In the present study, we have confirmed the authenticity of the notation based on the PTP1B inhibitory activity of farnesylated 2-arylbenzofurans. Specifically, two farnesylated 2-arylbenzofurans [morusalfurans B (2) and C (3)] showed strong inhibitory effects on PTP1B with IC(50) values of 8.92 and 7.26 µM, respectively, which was significantly higher than that of the positive controls [sodium orthovanadate (IC(50) = 15.10 µM) and ursolic acid (IC(50) = 11.34 µM)]. Besides, two 2-arylbenzofurans [morusalfurans A (1) and F (6)], one flavonoid [morusalnol B (9)], and one geranylated stilbene [morusibene A (11)] exhibited PTP1B inhibition with IC(50) values ranging from 11.02 to 26.56 µM. Kinetic studies revealed compounds 2, 3, 6, and 11 as mixed type PTP1B inhibitors, while 1 and 9 are known as noncompetitive. Molecular docking simulations demonstrated that these active compounds can bind with the respective catalytic or/and allosteric sites of PTP1B with negative binding energies and the results are in accordance with that of the kinetic studies. To the best of our knowledge, this is the first time, the PTP1B inhibitory activity of eleven compounds (1–11), as well as the mechanism of action underlying the effects on PTP1B enzyme of the active compounds, were investigated. In vitro and in silico results suggest that the farnesylated 2-arylbenzofurans from M. alba may potentially be utilized as an effective treatment therapy for type 2 diabetes mellitus and its associated complications. Pharmaceutical Society of Korea 2020-09-25 2020 /pmc/articles/PMC7518952/ /pubmed/32978714 http://dx.doi.org/10.1007/s12272-020-01269-4 Text en © The Pharmaceutical Society of Korea 2020 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Research Article Ha, Manh Tuan Shrestha, Srijan Tran, Thu Huong Kim, Jeong Ah Woo, Mi Hee Choi, Jae Sue Min, Byung Sun Inhibition of PTP1B by farnesylated 2-arylbenzofurans isolated from Morus alba root bark: unraveling the mechanism of inhibition based on in vitro and in silico studies |
title | Inhibition of PTP1B by farnesylated 2-arylbenzofurans isolated from Morus alba root bark: unraveling the mechanism of inhibition based on in vitro and in silico studies |
title_full | Inhibition of PTP1B by farnesylated 2-arylbenzofurans isolated from Morus alba root bark: unraveling the mechanism of inhibition based on in vitro and in silico studies |
title_fullStr | Inhibition of PTP1B by farnesylated 2-arylbenzofurans isolated from Morus alba root bark: unraveling the mechanism of inhibition based on in vitro and in silico studies |
title_full_unstemmed | Inhibition of PTP1B by farnesylated 2-arylbenzofurans isolated from Morus alba root bark: unraveling the mechanism of inhibition based on in vitro and in silico studies |
title_short | Inhibition of PTP1B by farnesylated 2-arylbenzofurans isolated from Morus alba root bark: unraveling the mechanism of inhibition based on in vitro and in silico studies |
title_sort | inhibition of ptp1b by farnesylated 2-arylbenzofurans isolated from morus alba root bark: unraveling the mechanism of inhibition based on in vitro and in silico studies |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518952/ https://www.ncbi.nlm.nih.gov/pubmed/32978714 http://dx.doi.org/10.1007/s12272-020-01269-4 |
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