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Synthesis, in vitro α-glucosidase inhibitory activities, and molecular dynamic simulations of novel 4-hydroxyquinolinone-hydrazones as potential antidiabetic agents

In the present study, new structural variants of 4-hydroxyquinolinone-hydrazones were designed and synthesized. The structure elucidation of the synthetic derivatives 6a–o was carried out using different spectroscopic techniques including FTIR, (1)H-NMR, (13)C-NMR, and elemental analysis, and their...

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Autores principales: Shayegan, Nahal, Haghipour, Sirous, Tanideh, Nader, Moazzam, Ali, Mojtabavi, Somayeh, Faramarzi, Mohammad Ali, Irajie, Cambyz, Parizad, Sara, Ansari, Shirin, Larijani, Bagher, Hosseini, Samanehsadat, Iraji, Aida, Mahdavi, Mohammad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113378/
https://www.ncbi.nlm.nih.gov/pubmed/37072431
http://dx.doi.org/10.1038/s41598-023-32889-7
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author Shayegan, Nahal
Haghipour, Sirous
Tanideh, Nader
Moazzam, Ali
Mojtabavi, Somayeh
Faramarzi, Mohammad Ali
Irajie, Cambyz
Parizad, Sara
Ansari, Shirin
Larijani, Bagher
Hosseini, Samanehsadat
Iraji, Aida
Mahdavi, Mohammad
author_facet Shayegan, Nahal
Haghipour, Sirous
Tanideh, Nader
Moazzam, Ali
Mojtabavi, Somayeh
Faramarzi, Mohammad Ali
Irajie, Cambyz
Parizad, Sara
Ansari, Shirin
Larijani, Bagher
Hosseini, Samanehsadat
Iraji, Aida
Mahdavi, Mohammad
author_sort Shayegan, Nahal
collection PubMed
description In the present study, new structural variants of 4-hydroxyquinolinone-hydrazones were designed and synthesized. The structure elucidation of the synthetic derivatives 6a–o was carried out using different spectroscopic techniques including FTIR, (1)H-NMR, (13)C-NMR, and elemental analysis, and their α-glucosidase inhibitory activity was also determined. The synthetic molecules 6a–o exhibited good α-glucosidase inhibition with IC(50) values ranging between 93.5 ± 0.6 to 575.6 ± 0.4 µM as compared to the standard acarbose (IC(50) = 752.0 ± 2.0 µM). Structure–activity relationships of this series were established which is mainly based on the position and nature of the substituent on the benzylidene ring. A kinetic study of the active compounds 6l and 6m as the most potent derivatives were also carried out to confirm the mode of inhibition. The binding interactions of the most active compounds within the active site of the enzyme were determined by molecular docking and molecular dynamic simulations.
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spelling pubmed-101133782023-04-20 Synthesis, in vitro α-glucosidase inhibitory activities, and molecular dynamic simulations of novel 4-hydroxyquinolinone-hydrazones as potential antidiabetic agents Shayegan, Nahal Haghipour, Sirous Tanideh, Nader Moazzam, Ali Mojtabavi, Somayeh Faramarzi, Mohammad Ali Irajie, Cambyz Parizad, Sara Ansari, Shirin Larijani, Bagher Hosseini, Samanehsadat Iraji, Aida Mahdavi, Mohammad Sci Rep Article In the present study, new structural variants of 4-hydroxyquinolinone-hydrazones were designed and synthesized. The structure elucidation of the synthetic derivatives 6a–o was carried out using different spectroscopic techniques including FTIR, (1)H-NMR, (13)C-NMR, and elemental analysis, and their α-glucosidase inhibitory activity was also determined. The synthetic molecules 6a–o exhibited good α-glucosidase inhibition with IC(50) values ranging between 93.5 ± 0.6 to 575.6 ± 0.4 µM as compared to the standard acarbose (IC(50) = 752.0 ± 2.0 µM). Structure–activity relationships of this series were established which is mainly based on the position and nature of the substituent on the benzylidene ring. A kinetic study of the active compounds 6l and 6m as the most potent derivatives were also carried out to confirm the mode of inhibition. The binding interactions of the most active compounds within the active site of the enzyme were determined by molecular docking and molecular dynamic simulations. Nature Publishing Group UK 2023-04-18 /pmc/articles/PMC10113378/ /pubmed/37072431 http://dx.doi.org/10.1038/s41598-023-32889-7 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
Shayegan, Nahal
Haghipour, Sirous
Tanideh, Nader
Moazzam, Ali
Mojtabavi, Somayeh
Faramarzi, Mohammad Ali
Irajie, Cambyz
Parizad, Sara
Ansari, Shirin
Larijani, Bagher
Hosseini, Samanehsadat
Iraji, Aida
Mahdavi, Mohammad
Synthesis, in vitro α-glucosidase inhibitory activities, and molecular dynamic simulations of novel 4-hydroxyquinolinone-hydrazones as potential antidiabetic agents
title Synthesis, in vitro α-glucosidase inhibitory activities, and molecular dynamic simulations of novel 4-hydroxyquinolinone-hydrazones as potential antidiabetic agents
title_full Synthesis, in vitro α-glucosidase inhibitory activities, and molecular dynamic simulations of novel 4-hydroxyquinolinone-hydrazones as potential antidiabetic agents
title_fullStr Synthesis, in vitro α-glucosidase inhibitory activities, and molecular dynamic simulations of novel 4-hydroxyquinolinone-hydrazones as potential antidiabetic agents
title_full_unstemmed Synthesis, in vitro α-glucosidase inhibitory activities, and molecular dynamic simulations of novel 4-hydroxyquinolinone-hydrazones as potential antidiabetic agents
title_short Synthesis, in vitro α-glucosidase inhibitory activities, and molecular dynamic simulations of novel 4-hydroxyquinolinone-hydrazones as potential antidiabetic agents
title_sort synthesis, in vitro α-glucosidase inhibitory activities, and molecular dynamic simulations of novel 4-hydroxyquinolinone-hydrazones as potential antidiabetic agents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113378/
https://www.ncbi.nlm.nih.gov/pubmed/37072431
http://dx.doi.org/10.1038/s41598-023-32889-7
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