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Design, synthesis, in vitro, and in silico evaluations of benzo[d]imidazole-amide-1,2,3-triazole-N-arylacetamide hybrids as new antidiabetic agents targeting α-glucosidase

α-Glucosidase as a carbohydrate-hydrolase enzyme is a crucial therapeutic target for type 2 diabetes. In this work, benzo[d]imidazole-amide containing 1,2,3-triazole-N-arylacetamide derivatives 8a–n were synthesized and evaluated for their inhibitory activity against α-glucosidase. In vitro α-glucos...

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Autores principales: Yousefnejad, Faeze, Mohammadi-Moghadam-Goozali, Mahyar, Sayahi, Mohammad Hosein, Halimi, Mohammad, Moazzam, Ali, Mohammadi-Khanaposhtani, Maryam, Mojtabavi, Somayeh, Asadi, Mehdi, Faramarzi, Mohammad Ali, Larijani, Bagher, Amanlou, Massoud, 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/PMC10390517/
https://www.ncbi.nlm.nih.gov/pubmed/37524733
http://dx.doi.org/10.1038/s41598-023-39424-8
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author Yousefnejad, Faeze
Mohammadi-Moghadam-Goozali, Mahyar
Sayahi, Mohammad Hosein
Halimi, Mohammad
Moazzam, Ali
Mohammadi-Khanaposhtani, Maryam
Mojtabavi, Somayeh
Asadi, Mehdi
Faramarzi, Mohammad Ali
Larijani, Bagher
Amanlou, Massoud
Mahdavi, Mohammad
author_facet Yousefnejad, Faeze
Mohammadi-Moghadam-Goozali, Mahyar
Sayahi, Mohammad Hosein
Halimi, Mohammad
Moazzam, Ali
Mohammadi-Khanaposhtani, Maryam
Mojtabavi, Somayeh
Asadi, Mehdi
Faramarzi, Mohammad Ali
Larijani, Bagher
Amanlou, Massoud
Mahdavi, Mohammad
author_sort Yousefnejad, Faeze
collection PubMed
description α-Glucosidase as a carbohydrate-hydrolase enzyme is a crucial therapeutic target for type 2 diabetes. In this work, benzo[d]imidazole-amide containing 1,2,3-triazole-N-arylacetamide derivatives 8a–n were synthesized and evaluated for their inhibitory activity against α-glucosidase. In vitro α-glucosidase inhibition assay demonstrated that more than half of the title compounds with IC(50) values in the range of 49.0–668.5 μM were more potent than standard inhibitor acarbose (IC(50) = 750.0 µM). The most promising inhibitor was N-2-methylphenylacetamid derivative 8c. Kinetic study revealed that compound 8c (K(i) = 40.0 µM) is a competitive inhibitor against α-glucosidase. Significantly, molecular docking and molecular dynamics studies on the most potent compound showed that this compound with a proper binding energy interacted with important amino acids of the α-glucosidase active site. Study on cytotoxicity of the most potent compounds 8c, 8e, and 8g demonstrated that these compounds did not show cytotoxic activity against the cancer and normal cell lines MCF-7 and HDF, respectively. Furthermore, the ADMET study predicted that compound 8c is likely to be orally active and non-cytotoxic.
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spelling pubmed-103905172023-08-02 Design, synthesis, in vitro, and in silico evaluations of benzo[d]imidazole-amide-1,2,3-triazole-N-arylacetamide hybrids as new antidiabetic agents targeting α-glucosidase Yousefnejad, Faeze Mohammadi-Moghadam-Goozali, Mahyar Sayahi, Mohammad Hosein Halimi, Mohammad Moazzam, Ali Mohammadi-Khanaposhtani, Maryam Mojtabavi, Somayeh Asadi, Mehdi Faramarzi, Mohammad Ali Larijani, Bagher Amanlou, Massoud Mahdavi, Mohammad Sci Rep Article α-Glucosidase as a carbohydrate-hydrolase enzyme is a crucial therapeutic target for type 2 diabetes. In this work, benzo[d]imidazole-amide containing 1,2,3-triazole-N-arylacetamide derivatives 8a–n were synthesized and evaluated for their inhibitory activity against α-glucosidase. In vitro α-glucosidase inhibition assay demonstrated that more than half of the title compounds with IC(50) values in the range of 49.0–668.5 μM were more potent than standard inhibitor acarbose (IC(50) = 750.0 µM). The most promising inhibitor was N-2-methylphenylacetamid derivative 8c. Kinetic study revealed that compound 8c (K(i) = 40.0 µM) is a competitive inhibitor against α-glucosidase. Significantly, molecular docking and molecular dynamics studies on the most potent compound showed that this compound with a proper binding energy interacted with important amino acids of the α-glucosidase active site. Study on cytotoxicity of the most potent compounds 8c, 8e, and 8g demonstrated that these compounds did not show cytotoxic activity against the cancer and normal cell lines MCF-7 and HDF, respectively. Furthermore, the ADMET study predicted that compound 8c is likely to be orally active and non-cytotoxic. Nature Publishing Group UK 2023-07-31 /pmc/articles/PMC10390517/ /pubmed/37524733 http://dx.doi.org/10.1038/s41598-023-39424-8 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/) .
spellingShingle Article
Yousefnejad, Faeze
Mohammadi-Moghadam-Goozali, Mahyar
Sayahi, Mohammad Hosein
Halimi, Mohammad
Moazzam, Ali
Mohammadi-Khanaposhtani, Maryam
Mojtabavi, Somayeh
Asadi, Mehdi
Faramarzi, Mohammad Ali
Larijani, Bagher
Amanlou, Massoud
Mahdavi, Mohammad
Design, synthesis, in vitro, and in silico evaluations of benzo[d]imidazole-amide-1,2,3-triazole-N-arylacetamide hybrids as new antidiabetic agents targeting α-glucosidase
title Design, synthesis, in vitro, and in silico evaluations of benzo[d]imidazole-amide-1,2,3-triazole-N-arylacetamide hybrids as new antidiabetic agents targeting α-glucosidase
title_full Design, synthesis, in vitro, and in silico evaluations of benzo[d]imidazole-amide-1,2,3-triazole-N-arylacetamide hybrids as new antidiabetic agents targeting α-glucosidase
title_fullStr Design, synthesis, in vitro, and in silico evaluations of benzo[d]imidazole-amide-1,2,3-triazole-N-arylacetamide hybrids as new antidiabetic agents targeting α-glucosidase
title_full_unstemmed Design, synthesis, in vitro, and in silico evaluations of benzo[d]imidazole-amide-1,2,3-triazole-N-arylacetamide hybrids as new antidiabetic agents targeting α-glucosidase
title_short Design, synthesis, in vitro, and in silico evaluations of benzo[d]imidazole-amide-1,2,3-triazole-N-arylacetamide hybrids as new antidiabetic agents targeting α-glucosidase
title_sort design, synthesis, in vitro, and in silico evaluations of benzo[d]imidazole-amide-1,2,3-triazole-n-arylacetamide hybrids as new antidiabetic agents targeting α-glucosidase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10390517/
https://www.ncbi.nlm.nih.gov/pubmed/37524733
http://dx.doi.org/10.1038/s41598-023-39424-8
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