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Novel 5-(Arylideneamino)-1H-Benzo[d]imidazole-2-thiols as Potent Anti-Diabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition, and Molecular Docking Studies
[Image: see text] A novel series of multifunctional benzimidazoles has been reported as potent inhibitors of α-glucosidase. The procedure relies on the synthesis of 5-amino-1H-benzo[d]imidazole-2-thiol 5 via the multistep reaction through 2-nitroaniline 1, benzene-1,2-diamine 2, 1H-benzo[d]imidazole...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9730482/ https://www.ncbi.nlm.nih.gov/pubmed/36506132 http://dx.doi.org/10.1021/acsomega.2c03854 |
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author | Ali, Sardar Ali, Mumtaz Khan, Ajmal Ullah, Saeed Waqas, Muhammad Al-Harrasi, Ahmed Latif, Abdul Ahmad, Manzoor Saadiq, Muhammad |
author_facet | Ali, Sardar Ali, Mumtaz Khan, Ajmal Ullah, Saeed Waqas, Muhammad Al-Harrasi, Ahmed Latif, Abdul Ahmad, Manzoor Saadiq, Muhammad |
author_sort | Ali, Sardar |
collection | PubMed |
description | [Image: see text] A novel series of multifunctional benzimidazoles has been reported as potent inhibitors of α-glucosidase. The procedure relies on the synthesis of 5-amino-1H-benzo[d]imidazole-2-thiol 5 via the multistep reaction through 2-nitroaniline 1, benzene-1,2-diamine 2, 1H-benzo[d]imidazole-2-thiol 3, and 5-nitro-1H-benzo[d]imidazole-2-thiol 4. Further treatment of 5 with aromatic aldehydes 6a–m provided access to the target 5-(arylideneamino)-1H-benzo[d]imidazole-2-thiols 7a–m. The results of the bioactivity assessment revealed all the compounds as excellent inhibitors of the enzyme (IC(50) range: 0.64 ± 0.05 μM to 343.10 ± 1.62 μM) than acarbose (873.34 ± 1.21). Among them, 7i was the most active inhibitor (IC(50): 0.64 ± 0.05 μM) followed by 7d (IC(50): 5.34 ± 0.16 μM), 7f (IC(50): 6.46 ± 0.30 μM), 7g (IC(50): 8.62 ± 0.19 μM), 7c (IC(50): 9.84 ± 0.08 μM), 7m (IC(50): 11.09 ± 0.79 μM), 7a (IC(50): 11.84 ± 0.26 μM), 7e (IC(50): 16.38 ± 0.53 μM), 7j (IC(50): 18.65 ± 0.74 μM), 7h (IC(50): 20.73 ± 0.59 μM), 7b (IC(50): 27.26 ± 0.30 μM), 7k (70.28 ± 1.52 μM) and finally 7l (IC(50): 343.10 ± 1.62 μM). Molecular docking revealed important interactions with the enzyme, thereby supporting the experimental findings. |
format | Online Article Text |
id | pubmed-9730482 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-97304822022-12-09 Novel 5-(Arylideneamino)-1H-Benzo[d]imidazole-2-thiols as Potent Anti-Diabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition, and Molecular Docking Studies Ali, Sardar Ali, Mumtaz Khan, Ajmal Ullah, Saeed Waqas, Muhammad Al-Harrasi, Ahmed Latif, Abdul Ahmad, Manzoor Saadiq, Muhammad ACS Omega [Image: see text] A novel series of multifunctional benzimidazoles has been reported as potent inhibitors of α-glucosidase. The procedure relies on the synthesis of 5-amino-1H-benzo[d]imidazole-2-thiol 5 via the multistep reaction through 2-nitroaniline 1, benzene-1,2-diamine 2, 1H-benzo[d]imidazole-2-thiol 3, and 5-nitro-1H-benzo[d]imidazole-2-thiol 4. Further treatment of 5 with aromatic aldehydes 6a–m provided access to the target 5-(arylideneamino)-1H-benzo[d]imidazole-2-thiols 7a–m. The results of the bioactivity assessment revealed all the compounds as excellent inhibitors of the enzyme (IC(50) range: 0.64 ± 0.05 μM to 343.10 ± 1.62 μM) than acarbose (873.34 ± 1.21). Among them, 7i was the most active inhibitor (IC(50): 0.64 ± 0.05 μM) followed by 7d (IC(50): 5.34 ± 0.16 μM), 7f (IC(50): 6.46 ± 0.30 μM), 7g (IC(50): 8.62 ± 0.19 μM), 7c (IC(50): 9.84 ± 0.08 μM), 7m (IC(50): 11.09 ± 0.79 μM), 7a (IC(50): 11.84 ± 0.26 μM), 7e (IC(50): 16.38 ± 0.53 μM), 7j (IC(50): 18.65 ± 0.74 μM), 7h (IC(50): 20.73 ± 0.59 μM), 7b (IC(50): 27.26 ± 0.30 μM), 7k (70.28 ± 1.52 μM) and finally 7l (IC(50): 343.10 ± 1.62 μM). Molecular docking revealed important interactions with the enzyme, thereby supporting the experimental findings. American Chemical Society 2022-11-23 /pmc/articles/PMC9730482/ /pubmed/36506132 http://dx.doi.org/10.1021/acsomega.2c03854 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Ali, Sardar Ali, Mumtaz Khan, Ajmal Ullah, Saeed Waqas, Muhammad Al-Harrasi, Ahmed Latif, Abdul Ahmad, Manzoor Saadiq, Muhammad Novel 5-(Arylideneamino)-1H-Benzo[d]imidazole-2-thiols as Potent Anti-Diabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition, and Molecular Docking Studies |
title | Novel 5-(Arylideneamino)-1H-Benzo[d]imidazole-2-thiols as
Potent Anti-Diabetic
Agents: Synthesis, In Vitro α-Glucosidase Inhibition,
and Molecular Docking Studies |
title_full | Novel 5-(Arylideneamino)-1H-Benzo[d]imidazole-2-thiols as
Potent Anti-Diabetic
Agents: Synthesis, In Vitro α-Glucosidase Inhibition,
and Molecular Docking Studies |
title_fullStr | Novel 5-(Arylideneamino)-1H-Benzo[d]imidazole-2-thiols as
Potent Anti-Diabetic
Agents: Synthesis, In Vitro α-Glucosidase Inhibition,
and Molecular Docking Studies |
title_full_unstemmed | Novel 5-(Arylideneamino)-1H-Benzo[d]imidazole-2-thiols as
Potent Anti-Diabetic
Agents: Synthesis, In Vitro α-Glucosidase Inhibition,
and Molecular Docking Studies |
title_short | Novel 5-(Arylideneamino)-1H-Benzo[d]imidazole-2-thiols as
Potent Anti-Diabetic
Agents: Synthesis, In Vitro α-Glucosidase Inhibition,
and Molecular Docking Studies |
title_sort | novel 5-(arylideneamino)-1h-benzo[d]imidazole-2-thiols as
potent anti-diabetic
agents: synthesis, in vitro α-glucosidase inhibition,
and molecular docking studies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9730482/ https://www.ncbi.nlm.nih.gov/pubmed/36506132 http://dx.doi.org/10.1021/acsomega.2c03854 |
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