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Structure—yeast α-glucosidase inhibitory activity relationship of 9-O-berberrubine carboxylates
Thirty-five 9-O-berberrubine carboxylate derivatives were synthesized and evaluated for yeast α-glucosidase inhibitory activity. All compounds demonstrated better inhibitory activities than the parent compounds berberine (BBR) and berberrubine (BBRB), and a positive control, acarbose. The structure–...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620162/ https://www.ncbi.nlm.nih.gov/pubmed/37914757 http://dx.doi.org/10.1038/s41598-023-45116-0 |
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author | Nguyen, Duy Vu Hengphasatporn, Kowit Danova, Ade Suroengrit, Aphinya Boonyasuppayakorn, Siwaporn Fujiki, Ryo Shigeta, Yasuteru Rungrotmongkol, Thanyada Chavasiri, Warinthorn |
author_facet | Nguyen, Duy Vu Hengphasatporn, Kowit Danova, Ade Suroengrit, Aphinya Boonyasuppayakorn, Siwaporn Fujiki, Ryo Shigeta, Yasuteru Rungrotmongkol, Thanyada Chavasiri, Warinthorn |
author_sort | Nguyen, Duy Vu |
collection | PubMed |
description | Thirty-five 9-O-berberrubine carboxylate derivatives were synthesized and evaluated for yeast α-glucosidase inhibitory activity. All compounds demonstrated better inhibitory activities than the parent compounds berberine (BBR) and berberrubine (BBRB), and a positive control, acarbose. The structure–activity correlation study indicated that most of the substituents on the benzoate moiety such as methoxy, hydroxy, methylenedioxy, benzyloxy, halogen, trifluoromethyl, nitro and alkyl can contribute to the activities except multi-methoxy, fluoro and cyano. In addition, replacing benzoate with naphthoate, cinnamate, piperate or diphenylacetate also led to an increase in inhibitory activities except with phenyl acetate. 9, 26, 27, 28 and 33 exhibited the most potent α-glucosidase inhibitory activities with the IC(50) values in the range of 1.61–2.67 μM. Kinetic study revealed that 9, 26, 28 and 33 interacted with the enzyme via competitive mode. These four compounds were also proved to be not cytotoxic at their IC(50) values. The competitive inhibition mechanism of these four compounds against yeast α-glucosidase was investigated using molecular docking and molecular dynamics simulations. The binding free energy calculations suggest that 26 exhibited the strongest binding affinity, and its binding stability is supported by hydrophobic interactions with D68, F157, F158 and F177. Therefore, 9, 26, 28 and 33 would be promising candidates for further studies of antidiabetic activity. |
format | Online Article Text |
id | pubmed-10620162 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-106201622023-11-03 Structure—yeast α-glucosidase inhibitory activity relationship of 9-O-berberrubine carboxylates Nguyen, Duy Vu Hengphasatporn, Kowit Danova, Ade Suroengrit, Aphinya Boonyasuppayakorn, Siwaporn Fujiki, Ryo Shigeta, Yasuteru Rungrotmongkol, Thanyada Chavasiri, Warinthorn Sci Rep Article Thirty-five 9-O-berberrubine carboxylate derivatives were synthesized and evaluated for yeast α-glucosidase inhibitory activity. All compounds demonstrated better inhibitory activities than the parent compounds berberine (BBR) and berberrubine (BBRB), and a positive control, acarbose. The structure–activity correlation study indicated that most of the substituents on the benzoate moiety such as methoxy, hydroxy, methylenedioxy, benzyloxy, halogen, trifluoromethyl, nitro and alkyl can contribute to the activities except multi-methoxy, fluoro and cyano. In addition, replacing benzoate with naphthoate, cinnamate, piperate or diphenylacetate also led to an increase in inhibitory activities except with phenyl acetate. 9, 26, 27, 28 and 33 exhibited the most potent α-glucosidase inhibitory activities with the IC(50) values in the range of 1.61–2.67 μM. Kinetic study revealed that 9, 26, 28 and 33 interacted with the enzyme via competitive mode. These four compounds were also proved to be not cytotoxic at their IC(50) values. The competitive inhibition mechanism of these four compounds against yeast α-glucosidase was investigated using molecular docking and molecular dynamics simulations. The binding free energy calculations suggest that 26 exhibited the strongest binding affinity, and its binding stability is supported by hydrophobic interactions with D68, F157, F158 and F177. Therefore, 9, 26, 28 and 33 would be promising candidates for further studies of antidiabetic activity. Nature Publishing Group UK 2023-11-01 /pmc/articles/PMC10620162/ /pubmed/37914757 http://dx.doi.org/10.1038/s41598-023-45116-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Nguyen, Duy Vu Hengphasatporn, Kowit Danova, Ade Suroengrit, Aphinya Boonyasuppayakorn, Siwaporn Fujiki, Ryo Shigeta, Yasuteru Rungrotmongkol, Thanyada Chavasiri, Warinthorn Structure—yeast α-glucosidase inhibitory activity relationship of 9-O-berberrubine carboxylates |
title | Structure—yeast α-glucosidase inhibitory activity relationship of 9-O-berberrubine carboxylates |
title_full | Structure—yeast α-glucosidase inhibitory activity relationship of 9-O-berberrubine carboxylates |
title_fullStr | Structure—yeast α-glucosidase inhibitory activity relationship of 9-O-berberrubine carboxylates |
title_full_unstemmed | Structure—yeast α-glucosidase inhibitory activity relationship of 9-O-berberrubine carboxylates |
title_short | Structure—yeast α-glucosidase inhibitory activity relationship of 9-O-berberrubine carboxylates |
title_sort | structure—yeast α-glucosidase inhibitory activity relationship of 9-o-berberrubine carboxylates |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620162/ https://www.ncbi.nlm.nih.gov/pubmed/37914757 http://dx.doi.org/10.1038/s41598-023-45116-0 |
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