α-amylase inhibition and in silico studies of novel naphtho[2,3-d]imidazole-4,9-dione linked N-acyl hydrazones
Aim: To enrich the pool of α-amylase inhibitors to manage Type 2 diabetes. Methods: Synthesis, conformational study, α-amylase inhibitory action and various in silico studies of novel N'-(arylbenzylidene)-2-(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d]imidazol-1-yl)acetohydrazides carried out. Results: Compound H6 demonstrated the highest activity (IC50 = 0.0437 μmol mL-1) among the tested compounds. Structure-activity relationship study suggested that variable substitution at the aryl ring has a pivotal role in determining the inhibitory action of tested compounds. Docking simulations of the most active compound (H6) confirmed its interaction potential with active site residues of A. oryzae α-amylase. The root-mean-square deviation fluctuations substantiated the stability of protein-ligand complex. Absorption, distribution, metabolism and excretion prediction revealed optimal values for absorption, distribution, metabolism and excretion parameters. Conclusion: The developed molecules could be beneficial for the development of novel α-amylase inhibitors to treat Type 2 diabetes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Future medicinal chemistry - 15(2023), 16 vom: 22. Aug., Seite 1511-1525 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Devi, Meena [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.10.2023 Date Revised 18.10.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/fmc-2023-0158 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361093063 |
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| 245 | 1 | 0 | |a α-amylase inhibition and in silico studies of novel naphtho[2,3-d]imidazole-4,9-dione linked N-acyl hydrazones |
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| 500 | |a Date Completed 11.10.2023 | ||
| 500 | |a Date Revised 18.10.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Aim: To enrich the pool of α-amylase inhibitors to manage Type 2 diabetes. Methods: Synthesis, conformational study, α-amylase inhibitory action and various in silico studies of novel N'-(arylbenzylidene)-2-(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d]imidazol-1-yl)acetohydrazides carried out. Results: Compound H6 demonstrated the highest activity (IC50 = 0.0437 μmol mL-1) among the tested compounds. Structure-activity relationship study suggested that variable substitution at the aryl ring has a pivotal role in determining the inhibitory action of tested compounds. Docking simulations of the most active compound (H6) confirmed its interaction potential with active site residues of A. oryzae α-amylase. The root-mean-square deviation fluctuations substantiated the stability of protein-ligand complex. Absorption, distribution, metabolism and excretion prediction revealed optimal values for absorption, distribution, metabolism and excretion parameters. Conclusion: The developed molecules could be beneficial for the development of novel α-amylase inhibitors to treat Type 2 diabetes | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a 2,3-diamino-1,4-naphthoquinone | |
| 650 | 4 | |a In silico studies | |
| 650 | 4 | |a N-acyl hydrazones | |
| 650 | 4 | |a naphtho[2,3-d]imidazole-4,9-dione | |
| 650 | 4 | |a α-amylase | |
| 650 | 7 | |a Hydrazones |2 NLM | |
| 650 | 7 | |a alpha-Amylases |2 NLM | |
| 650 | 7 | |a EC 3.2.1.1 |2 NLM | |
| 650 | 7 | |a Imidazoles |2 NLM | |
| 700 | 1 | |a Kumar, Parvin |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Rahul |e verfasserin |4 aut | |
| 700 | 1 | |a Sindhu, Jayant |e verfasserin |4 aut | |
| 700 | 1 | |a Kumar, Ashwani |e verfasserin |4 aut | |
| 700 | 1 | |a Lal, Sohan |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Devender |e verfasserin |4 aut | |
| 700 | 1 | |a Kumar, Harish |e verfasserin |4 aut | |
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