Multicomponent diastereoselective synthesis of tetrahydropyridines as α-amylase and α-glucosidase enzymes inhibitors
Background: Researchers seeking new drug candidates to treat diabetes mellitus have been exploring bioactive molecules found in nature, particularly tetrahydropyridines (THPs). Methods: A library of THPs (1-31) were synthesized via a one-pot multicomponent reaction and investigated for their inhibition potential against α-glucosidase and α-amylase enzymes. Results: A nitrophenyl-substituted compound 5 with IC50 values of 0.15 ± 0.01 and 1.10 ± 0.04 μM, and a Km value of 1.30 mg/ml was identified as the most significant α-glucosidase and α-amylase inhibitor, respectively. Kinetic studies revealed the competitive mode of inhibition, and docking studies revealed that compound 5 binds to the enzyme by establishing hydrophobic and hydrophilic interactions and a salt bridge interaction with His279. Conclusion: These molecules may be a potential drug candidate for diabetes in the future.
| 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), 15 vom: 14. Aug., Seite 1343-1368 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Saleem, Faiza [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-2023-0073 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361485808 |
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| 100 | 1 | |a Saleem, Faiza |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Multicomponent diastereoselective synthesis of tetrahydropyridines as α-amylase and α-glucosidase enzymes inhibitors |
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| 500 | |a Date Revised 18.10.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Background: Researchers seeking new drug candidates to treat diabetes mellitus have been exploring bioactive molecules found in nature, particularly tetrahydropyridines (THPs). Methods: A library of THPs (1-31) were synthesized via a one-pot multicomponent reaction and investigated for their inhibition potential against α-glucosidase and α-amylase enzymes. Results: A nitrophenyl-substituted compound 5 with IC50 values of 0.15 ± 0.01 and 1.10 ± 0.04 μM, and a Km value of 1.30 mg/ml was identified as the most significant α-glucosidase and α-amylase inhibitor, respectively. Kinetic studies revealed the competitive mode of inhibition, and docking studies revealed that compound 5 binds to the enzyme by establishing hydrophobic and hydrophilic interactions and a salt bridge interaction with His279. Conclusion: These molecules may be a potential drug candidate for diabetes in the future | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a in silico | |
| 650 | 4 | |a in vitro | |
| 650 | 4 | |a kinetic studies | |
| 650 | 4 | |a pyridine | |
| 650 | 4 | |a α-amylase activity | |
| 650 | 4 | |a α-glucosidase activity | |
| 650 | 7 | |a alpha-Amylases |2 NLM | |
| 650 | 7 | |a EC 3.2.1.1 |2 NLM | |
| 650 | 7 | |a alpha-Glucosidases |2 NLM | |
| 650 | 7 | |a EC 3.2.1.20 |2 NLM | |
| 650 | 7 | |a Glycoside Hydrolase Inhibitors |2 NLM | |
| 700 | 1 | |a Shamim, Fariha |e verfasserin |4 aut | |
| 700 | 1 | |a Özil, Musa |e verfasserin |4 aut | |
| 700 | 1 | |a Baltaş, Nimet |e verfasserin |4 aut | |
| 700 | 1 | |a Salar, Uzma |e verfasserin |4 aut | |
| 700 | 1 | |a Ashraf, Sajda |e verfasserin |4 aut | |
| 700 | 1 | |a Ul-Haq, Zaheer |e verfasserin |4 aut | |
| 700 | 1 | |a Taha, Muhammad |e verfasserin |4 aut | |
| 700 | 1 | |a Solangi, Mehwish |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Khalid Mohammed |e verfasserin |4 aut | |
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