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Synthesis, α-Glucosidase inhibitory activity and docking studies of Novel Ethyl 1,2,3-triazol-4-ylmethylthio-5,6-diphenylpyridazine-4-carboxylate derivatives
In this work, a novel series of pyridazine-triazole hybrid molecules were prepared and evaluated as inhibitors of rat intestinal α-glucosidase enzyme. Amongst all newly synthesized compounds, 10k showed good inhibition in the series with IC(50) value of 1.7 µM which is 100 folds stronger than positi...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10294378/ https://www.ncbi.nlm.nih.gov/pubmed/37365646 http://dx.doi.org/10.1186/s13065-023-00973-8 |
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author | Firoozpour, Loghman Moghimi, Setareh Salarinejad, Somayeh Toolabi, Mahsa Rafsanjani, Mahdi Pakrad, Roya Salmani, Farzaneh Shokrolahi, Seyed Mohammad Sadat Ebrahimi, Seyed Esmail Karima, Saeed Foroumadi, Alireza |
author_facet | Firoozpour, Loghman Moghimi, Setareh Salarinejad, Somayeh Toolabi, Mahsa Rafsanjani, Mahdi Pakrad, Roya Salmani, Farzaneh Shokrolahi, Seyed Mohammad Sadat Ebrahimi, Seyed Esmail Karima, Saeed Foroumadi, Alireza |
author_sort | Firoozpour, Loghman |
collection | PubMed |
description | In this work, a novel series of pyridazine-triazole hybrid molecules were prepared and evaluated as inhibitors of rat intestinal α-glucosidase enzyme. Amongst all newly synthesized compounds, 10k showed good inhibition in the series with IC(50) value of 1.7 µM which is 100 folds stronger than positive control, acarbose. The cytotoxicity revealed that this compound is not toxic against normal cell line, HDF. The docking studies showed that triazole ring plays an important role in the binding interactions with the active site. The insertion of compound 10k into the active pocket of α-glucosidase and formation of hydrogen bonds with Leu677 was observed from docking studies. The kinetic studies revealed that this compound has uncompetitive mode of inhibition against α-glucosidase enzyme. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13065-023-00973-8. |
format | Online Article Text |
id | pubmed-10294378 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-102943782023-06-28 Synthesis, α-Glucosidase inhibitory activity and docking studies of Novel Ethyl 1,2,3-triazol-4-ylmethylthio-5,6-diphenylpyridazine-4-carboxylate derivatives Firoozpour, Loghman Moghimi, Setareh Salarinejad, Somayeh Toolabi, Mahsa Rafsanjani, Mahdi Pakrad, Roya Salmani, Farzaneh Shokrolahi, Seyed Mohammad Sadat Ebrahimi, Seyed Esmail Karima, Saeed Foroumadi, Alireza BMC Chem Research In this work, a novel series of pyridazine-triazole hybrid molecules were prepared and evaluated as inhibitors of rat intestinal α-glucosidase enzyme. Amongst all newly synthesized compounds, 10k showed good inhibition in the series with IC(50) value of 1.7 µM which is 100 folds stronger than positive control, acarbose. The cytotoxicity revealed that this compound is not toxic against normal cell line, HDF. The docking studies showed that triazole ring plays an important role in the binding interactions with the active site. The insertion of compound 10k into the active pocket of α-glucosidase and formation of hydrogen bonds with Leu677 was observed from docking studies. The kinetic studies revealed that this compound has uncompetitive mode of inhibition against α-glucosidase enzyme. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13065-023-00973-8. Springer International Publishing 2023-06-26 /pmc/articles/PMC10294378/ /pubmed/37365646 http://dx.doi.org/10.1186/s13065-023-00973-8 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/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Firoozpour, Loghman Moghimi, Setareh Salarinejad, Somayeh Toolabi, Mahsa Rafsanjani, Mahdi Pakrad, Roya Salmani, Farzaneh Shokrolahi, Seyed Mohammad Sadat Ebrahimi, Seyed Esmail Karima, Saeed Foroumadi, Alireza Synthesis, α-Glucosidase inhibitory activity and docking studies of Novel Ethyl 1,2,3-triazol-4-ylmethylthio-5,6-diphenylpyridazine-4-carboxylate derivatives |
title | Synthesis, α-Glucosidase inhibitory activity and docking studies of Novel Ethyl 1,2,3-triazol-4-ylmethylthio-5,6-diphenylpyridazine-4-carboxylate derivatives |
title_full | Synthesis, α-Glucosidase inhibitory activity and docking studies of Novel Ethyl 1,2,3-triazol-4-ylmethylthio-5,6-diphenylpyridazine-4-carboxylate derivatives |
title_fullStr | Synthesis, α-Glucosidase inhibitory activity and docking studies of Novel Ethyl 1,2,3-triazol-4-ylmethylthio-5,6-diphenylpyridazine-4-carboxylate derivatives |
title_full_unstemmed | Synthesis, α-Glucosidase inhibitory activity and docking studies of Novel Ethyl 1,2,3-triazol-4-ylmethylthio-5,6-diphenylpyridazine-4-carboxylate derivatives |
title_short | Synthesis, α-Glucosidase inhibitory activity and docking studies of Novel Ethyl 1,2,3-triazol-4-ylmethylthio-5,6-diphenylpyridazine-4-carboxylate derivatives |
title_sort | synthesis, α-glucosidase inhibitory activity and docking studies of novel ethyl 1,2,3-triazol-4-ylmethylthio-5,6-diphenylpyridazine-4-carboxylate derivatives |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10294378/ https://www.ncbi.nlm.nih.gov/pubmed/37365646 http://dx.doi.org/10.1186/s13065-023-00973-8 |
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