Clodronic Acid has Strong Inhibitory Interactions with the Urease Enzyme of Helicobacter Pylori : Computer-aided Design and in vitro Confirmation
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
BACKGROUND: Helicobacter Pylori (HP) infection could lead to various gastrointestinal diseases. Urease is the most important virulence factor of HP. It protects the bacterium against gastric acid.
OBJECTIVE: Therefore, we aimed to design urease inhibitors as drugs against HP infection.
METHODS: The DrugBank-approved library was assigned with 3D conformations and the structure of the urease was prepared. Using a re-docking strategy, the proper settings were determined for docking by PyRx and GOLD software. Virtual screening was performed to select the best inhibitory drugs based on binding affinity, FitnessScore, and binding orientation to critical amino acids of the active site. The best inhibitory drug was then evaluated by IC50 and the diameter of the zone of inhibition for bacterial growth.
RESULTS: The structures of prepared drugs were screened against urease structure using the determined settings. Clodronic acid was determined to be the best-identified drug, due to higher PyRx binding energy, better GOLD FitnessScore, and interaction with critical amino acids of urease. In vitro results were also in line with the computational data. IC50 values of Clodronic acid and Acetohydroxamic Acid (AHA) were 29.78 ± 1.13 and 47.29 ± 2.06 μg/ml, respectively. Diameters of the zones of inhibition were 18 and 15 mm for Clodronic acid and AHA, respectively.
CONCLUSION: Clodronic acid has better HP urease inhibition potential than AHA. Given its approved status, the development of a repurposed drug based on Clodronic acid would require less time and cost. Further, in vivo studies would unveil the efficacy of Clodronic acid as a urease inhibitor.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
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| Enthalten in: |
Current computer-aided drug design - (2023) vom: 10. Nov. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fath, Mohsen Karami [VerfasserIn] |
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| Links: |
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| Themen: |
Approved small molecule drugs |
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| Anmerkungen: |
Date Revised 14.11.2023 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.2174/0115734099271837231026064439 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364495499 |
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| 500 | |a Date Revised 14.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a BACKGROUND: Helicobacter Pylori (HP) infection could lead to various gastrointestinal diseases. Urease is the most important virulence factor of HP. It protects the bacterium against gastric acid | ||
| 520 | |a OBJECTIVE: Therefore, we aimed to design urease inhibitors as drugs against HP infection | ||
| 520 | |a METHODS: The DrugBank-approved library was assigned with 3D conformations and the structure of the urease was prepared. Using a re-docking strategy, the proper settings were determined for docking by PyRx and GOLD software. Virtual screening was performed to select the best inhibitory drugs based on binding affinity, FitnessScore, and binding orientation to critical amino acids of the active site. The best inhibitory drug was then evaluated by IC50 and the diameter of the zone of inhibition for bacterial growth | ||
| 520 | |a RESULTS: The structures of prepared drugs were screened against urease structure using the determined settings. Clodronic acid was determined to be the best-identified drug, due to higher PyRx binding energy, better GOLD FitnessScore, and interaction with critical amino acids of urease. In vitro results were also in line with the computational data. IC50 values of Clodronic acid and Acetohydroxamic Acid (AHA) were 29.78 ± 1.13 and 47.29 ± 2.06 μg/ml, respectively. Diameters of the zones of inhibition were 18 and 15 mm for Clodronic acid and AHA, respectively | ||
| 520 | |a CONCLUSION: Clodronic acid has better HP urease inhibition potential than AHA. Given its approved status, the development of a repurposed drug based on Clodronic acid would require less time and cost. Further, in vivo studies would unveil the efficacy of Clodronic acid as a urease inhibitor | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Helicobacter pylori | |
| 650 | 4 | |a approved small molecule drugs | |
| 650 | 4 | |a clodronic acid. | |
| 650 | 4 | |a docking | |
| 650 | 4 | |a urease | |
| 700 | 1 | |a Khalili, Saeed |e verfasserin |4 aut | |
| 700 | 1 | |a Boojar, Masoud Mashhadi Akbar |e verfasserin |4 aut | |
| 700 | 1 | |a Hashemi, Zahra Sadat |e verfasserin |4 aut | |
| 700 | 1 | |a Zarei, Mahboubeh |e verfasserin |4 aut | |
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