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Isolation, semi-synthesis, docking-based prediction, and bioassay-based activity of Dolichandrone spathacea iridoids: new catalpol derivatives as glucosidase inhibitors

Dolichandrone spathacea iridoids are promising anti-diabetic inhibitors towards α-glucosidase protein (PDB-3W37) and oligo-1,6-glucosidase protein (PDB-3AJ7). Five catalpol iridoids (1, 2, 10, 13, 14) were isolated from mangrove plant D. spathacea, and their derivatives (3, 4, 5, 6, 7, 8, 9, 11, 12,...

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Autores principales: Phuong Thao, Tran Thi, Bui, Thanh Q., Quy, Phan Tu, Bao, Nguyen Chi, Van Loc, Tran, Van Chien, Tran, Chi, Nguyen Linh, Van Tuan, Nguyen, Van Sung, Tran, Ai Nhung, Nguyen Thi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8696980/
https://www.ncbi.nlm.nih.gov/pubmed/35423771
http://dx.doi.org/10.1039/d1ra00441g
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author Phuong Thao, Tran Thi
Bui, Thanh Q.
Quy, Phan Tu
Bao, Nguyen Chi
Van Loc, Tran
Van Chien, Tran
Chi, Nguyen Linh
Van Tuan, Nguyen
Van Sung, Tran
Ai Nhung, Nguyen Thi
author_facet Phuong Thao, Tran Thi
Bui, Thanh Q.
Quy, Phan Tu
Bao, Nguyen Chi
Van Loc, Tran
Van Chien, Tran
Chi, Nguyen Linh
Van Tuan, Nguyen
Van Sung, Tran
Ai Nhung, Nguyen Thi
author_sort Phuong Thao, Tran Thi
collection PubMed
description Dolichandrone spathacea iridoids are promising anti-diabetic inhibitors towards α-glucosidase protein (PDB-3W37) and oligo-1,6-glucosidase protein (PDB-3AJ7). Five catalpol iridoids (1, 2, 10, 13, 14) were isolated from mangrove plant D. spathacea, and their derivatives (3, 4, 5, 6, 7, 8, 9, 11, 12, 15) were obtained from reduction, acetylation, O-alkylation, acetonisation, or hydrolysation starting from naturally isolated compounds. They were identified by spectral methods such as IR, MS, and 1D and 2D NMR. Their glucosidase-related (3W37 and 3AJ7) inhibitability and physiological compatibility were predicted by molecular docking simulation and prescreened based on Lipinski's rule of five. Experimental α-glucosidase inhibition of 1–15 was evaluated using enzyme assays. Compounds 3, 4, 5, 6, and 9 are new iridoid derivatives, introduced to the literature for the first time, while all fifteen compounds 1–15 are studied for molecular docking for the first time. Regarding protein 3W37, the five strongest predicted inhibitors assemble in the order 2 > 10 > 1 > 9 > 14. In respect to 3AJ7, the corresponding order is 14 > 2 > 10 > 5 > 1 = 9. Lipinski's criteria suggest 10 as the candidate with the most potential for oral administration. The in vitro bioassay revealed that compound 10 is the most effective inhibitor with a respective IC(50) value of 0.05 μM, in the order 10 > 2 > 14 > 13 > 1. The computational and experimental results show good consistency. The study opens an alternative approach for diabetes treatment based on inhibitability of natural and semi-synthesised catalpol iridoid derivatives towards carbohydrate-hydrolases.
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spelling pubmed-86969802022-04-13 Isolation, semi-synthesis, docking-based prediction, and bioassay-based activity of Dolichandrone spathacea iridoids: new catalpol derivatives as glucosidase inhibitors Phuong Thao, Tran Thi Bui, Thanh Q. Quy, Phan Tu Bao, Nguyen Chi Van Loc, Tran Van Chien, Tran Chi, Nguyen Linh Van Tuan, Nguyen Van Sung, Tran Ai Nhung, Nguyen Thi RSC Adv Chemistry Dolichandrone spathacea iridoids are promising anti-diabetic inhibitors towards α-glucosidase protein (PDB-3W37) and oligo-1,6-glucosidase protein (PDB-3AJ7). Five catalpol iridoids (1, 2, 10, 13, 14) were isolated from mangrove plant D. spathacea, and their derivatives (3, 4, 5, 6, 7, 8, 9, 11, 12, 15) were obtained from reduction, acetylation, O-alkylation, acetonisation, or hydrolysation starting from naturally isolated compounds. They were identified by spectral methods such as IR, MS, and 1D and 2D NMR. Their glucosidase-related (3W37 and 3AJ7) inhibitability and physiological compatibility were predicted by molecular docking simulation and prescreened based on Lipinski's rule of five. Experimental α-glucosidase inhibition of 1–15 was evaluated using enzyme assays. Compounds 3, 4, 5, 6, and 9 are new iridoid derivatives, introduced to the literature for the first time, while all fifteen compounds 1–15 are studied for molecular docking for the first time. Regarding protein 3W37, the five strongest predicted inhibitors assemble in the order 2 > 10 > 1 > 9 > 14. In respect to 3AJ7, the corresponding order is 14 > 2 > 10 > 5 > 1 = 9. Lipinski's criteria suggest 10 as the candidate with the most potential for oral administration. The in vitro bioassay revealed that compound 10 is the most effective inhibitor with a respective IC(50) value of 0.05 μM, in the order 10 > 2 > 14 > 13 > 1. The computational and experimental results show good consistency. The study opens an alternative approach for diabetes treatment based on inhibitability of natural and semi-synthesised catalpol iridoid derivatives towards carbohydrate-hydrolases. The Royal Society of Chemistry 2021-03-23 /pmc/articles/PMC8696980/ /pubmed/35423771 http://dx.doi.org/10.1039/d1ra00441g Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Phuong Thao, Tran Thi
Bui, Thanh Q.
Quy, Phan Tu
Bao, Nguyen Chi
Van Loc, Tran
Van Chien, Tran
Chi, Nguyen Linh
Van Tuan, Nguyen
Van Sung, Tran
Ai Nhung, Nguyen Thi
Isolation, semi-synthesis, docking-based prediction, and bioassay-based activity of Dolichandrone spathacea iridoids: new catalpol derivatives as glucosidase inhibitors
title Isolation, semi-synthesis, docking-based prediction, and bioassay-based activity of Dolichandrone spathacea iridoids: new catalpol derivatives as glucosidase inhibitors
title_full Isolation, semi-synthesis, docking-based prediction, and bioassay-based activity of Dolichandrone spathacea iridoids: new catalpol derivatives as glucosidase inhibitors
title_fullStr Isolation, semi-synthesis, docking-based prediction, and bioassay-based activity of Dolichandrone spathacea iridoids: new catalpol derivatives as glucosidase inhibitors
title_full_unstemmed Isolation, semi-synthesis, docking-based prediction, and bioassay-based activity of Dolichandrone spathacea iridoids: new catalpol derivatives as glucosidase inhibitors
title_short Isolation, semi-synthesis, docking-based prediction, and bioassay-based activity of Dolichandrone spathacea iridoids: new catalpol derivatives as glucosidase inhibitors
title_sort isolation, semi-synthesis, docking-based prediction, and bioassay-based activity of dolichandrone spathacea iridoids: new catalpol derivatives as glucosidase inhibitors
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8696980/
https://www.ncbi.nlm.nih.gov/pubmed/35423771
http://dx.doi.org/10.1039/d1ra00441g
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