Clodronic Acid has Strong Inhibitory Interactions with the Urease Enzyme of Helicobacter Pylori: Computer-aided Design and in vitro Confirmation

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.

 

Comments:

Your study on designing urease inhibitors to combat Helicobacter pylori infection sounds promising! Clodronic acid appears to be a strong candidate due to its favorable binding energy, FitnessScore, and interactions with critical amino acids of urease. The in vitro results showing lower IC50 and larger zones of inhibition compared to Acetohydroxamic Acid (AHA) further support its potential.

The fact that Clodronic acid is already approved could significantly expedite the process of repurposing it as a drug against H. pylori infection. Still, further in vivo studies will be crucial to validate its efficacy as a urease inhibitor within a living organism. This step will offer a more comprehensive understanding of its effectiveness and safety profile.

Your approach combining computational screening with in vitro assays showcases a well-rounded methodology for identifying potential drug candidates. Should you proceed with further research, refining Clodronic acid as a targeted therapy for H. pylori infection seems promising.

Related Products

Cat.No.	Product Name	Information
S4602	Acetohydroxamic acid	Acetohydroxamic acid is an Urease Inhibitor. In the urine, it acts as an antagonist of the bacterial enzyme urease.

Related Targets

Bacterial