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Synthesis and structure–activity relationship studies of benzimidazole-thioquinoline derivatives as α-glucosidase inhibitors

In this article, different s-substituted benzimidazole-thioquinoline derivatives were designed, synthesized, and evaluated for their possible α-glucosidase inhibitory activities. The most active compound in this series, 6j (X = 4-bromobenzyl) exhibited significant potency with an IC(50) value of 28....

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Autores principales: Moghadam Farid, Sara, Noori, Milad, Nazari Montazer, Mohammad, Khalili Ghomi, Minoo, Mollazadeh, Marjan, Dastyafteh, Navid, Irajie, Cambyz, Zomorodian, Kamiar, Mirfazli, Seyedeh Sara, Mojtabavi, Somayeh, Faramarzi, Mohammad Ali, Larijani, Bagher, 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/PMC10020548/
https://www.ncbi.nlm.nih.gov/pubmed/36928433
http://dx.doi.org/10.1038/s41598-023-31080-2
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author Moghadam Farid, Sara
Noori, Milad
Nazari Montazer, Mohammad
Khalili Ghomi, Minoo
Mollazadeh, Marjan
Dastyafteh, Navid
Irajie, Cambyz
Zomorodian, Kamiar
Mirfazli, Seyedeh Sara
Mojtabavi, Somayeh
Faramarzi, Mohammad Ali
Larijani, Bagher
Iraji, Aida
Mahdavi, Mohammad
author_facet Moghadam Farid, Sara
Noori, Milad
Nazari Montazer, Mohammad
Khalili Ghomi, Minoo
Mollazadeh, Marjan
Dastyafteh, Navid
Irajie, Cambyz
Zomorodian, Kamiar
Mirfazli, Seyedeh Sara
Mojtabavi, Somayeh
Faramarzi, Mohammad Ali
Larijani, Bagher
Iraji, Aida
Mahdavi, Mohammad
author_sort Moghadam Farid, Sara
collection PubMed
description In this article, different s-substituted benzimidazole-thioquinoline derivatives were designed, synthesized, and evaluated for their possible α-glucosidase inhibitory activities. The most active compound in this series, 6j (X = 4-bromobenzyl) exhibited significant potency with an IC(50) value of 28.0 ± 0.6 µM compared to acarbose as the positive control with an IC(50) value of 750.0 µM. The kinetic study showed a competitive inhibition pattern against α-glucosidase for the 6j derivative. Also, the molecular dynamic simulations were performed to determine key interactions between compounds and the targeted enzyme. The in silico pharmacodynamics and ADMET properties were executed to illustrate the druggability of the novel derivatives. In general, it can be concluded that these derivatives can serve as promising leads to the design of potential α-glucosidase inhibitors.
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spelling pubmed-100205482023-03-18 Synthesis and structure–activity relationship studies of benzimidazole-thioquinoline derivatives as α-glucosidase inhibitors Moghadam Farid, Sara Noori, Milad Nazari Montazer, Mohammad Khalili Ghomi, Minoo Mollazadeh, Marjan Dastyafteh, Navid Irajie, Cambyz Zomorodian, Kamiar Mirfazli, Seyedeh Sara Mojtabavi, Somayeh Faramarzi, Mohammad Ali Larijani, Bagher Iraji, Aida Mahdavi, Mohammad Sci Rep Article In this article, different s-substituted benzimidazole-thioquinoline derivatives were designed, synthesized, and evaluated for their possible α-glucosidase inhibitory activities. The most active compound in this series, 6j (X = 4-bromobenzyl) exhibited significant potency with an IC(50) value of 28.0 ± 0.6 µM compared to acarbose as the positive control with an IC(50) value of 750.0 µM. The kinetic study showed a competitive inhibition pattern against α-glucosidase for the 6j derivative. Also, the molecular dynamic simulations were performed to determine key interactions between compounds and the targeted enzyme. The in silico pharmacodynamics and ADMET properties were executed to illustrate the druggability of the novel derivatives. In general, it can be concluded that these derivatives can serve as promising leads to the design of potential α-glucosidase inhibitors. Nature Publishing Group UK 2023-03-16 /pmc/articles/PMC10020548/ /pubmed/36928433 http://dx.doi.org/10.1038/s41598-023-31080-2 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
Moghadam Farid, Sara
Noori, Milad
Nazari Montazer, Mohammad
Khalili Ghomi, Minoo
Mollazadeh, Marjan
Dastyafteh, Navid
Irajie, Cambyz
Zomorodian, Kamiar
Mirfazli, Seyedeh Sara
Mojtabavi, Somayeh
Faramarzi, Mohammad Ali
Larijani, Bagher
Iraji, Aida
Mahdavi, Mohammad
Synthesis and structure–activity relationship studies of benzimidazole-thioquinoline derivatives as α-glucosidase inhibitors
title Synthesis and structure–activity relationship studies of benzimidazole-thioquinoline derivatives as α-glucosidase inhibitors
title_full Synthesis and structure–activity relationship studies of benzimidazole-thioquinoline derivatives as α-glucosidase inhibitors
title_fullStr Synthesis and structure–activity relationship studies of benzimidazole-thioquinoline derivatives as α-glucosidase inhibitors
title_full_unstemmed Synthesis and structure–activity relationship studies of benzimidazole-thioquinoline derivatives as α-glucosidase inhibitors
title_short Synthesis and structure–activity relationship studies of benzimidazole-thioquinoline derivatives as α-glucosidase inhibitors
title_sort synthesis and structure–activity relationship studies of benzimidazole-thioquinoline derivatives as α-glucosidase inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10020548/
https://www.ncbi.nlm.nih.gov/pubmed/36928433
http://dx.doi.org/10.1038/s41598-023-31080-2
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