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image of Multistep In Silico Pipeline for Targeting FimH Adhesin with Chalcones as Anti-Adhesion Therapeutics

Abstract

Introduction

FimH, a bacterial adhesin on (UPEC), facilitates host cell attachment and initiates Urinary Tract Infections (UTIs). With rising antibiotic resistance, alternative therapeutics targeting bacterial adhesion are urgently needed. This study investigates chalcone derivatives as potential anti-adhesive agents against FimH, aiming to inhibit bacterial colonization and reduce virulence through an approach.

Methods

A total of 200 chalcone derivatives were subjected to toxicity screening using ProTox-II, followed by molecular docking using MVD 6.0 and AutoDock Vina against FimH (PDB IDs: 5AAP and 4XO8). The most promising compounds underwent structural pharmacophore modeling in LigandScout, pharmacokinetic profiling SwissADME and PreADMET, and further validation through molecular dynamics simulations and MMPBSA free energy calculations.

Results

Chalcones 103, 122, and 137 showed strong binding affinities, with highly negative MolDock scores surpassing native ligands. Key residues such as Gln133, Asp47, and Phe1 were identified as essential for hydrogen bonding. Pharmacokinetic profiles revealed high gastrointestinal absorption, BBB permeability, and compliance with major drug-likeness filters. RMSF analysis indicated 4XO8’s structural rigidity, while MMPBSA confirmed strong binding energies, particularly for the 4XO8-137 complex.

Discussion

These findings suggest chalcone derivatives, especially Chalcone 137, demonstrate promising anti-adhesive properties, structural stability, and favourable pharmacokinetics, making them viable candidates for further drug development.

Conclusion

Chalcones 103, 122, and 137, particularly the 4XO8-137 complex, exhibit strong therapeutic potential as non-antibiotic anti-adhesion agents against UTI-causing , warranting further experimental validation and .

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2025-10-23
2025-12-16

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Multistep In Silico Pipeline for Targeting FimH Adhesin with Chalcones as Anti-Adhesion Therapeutics
Bentham Science Publishers ; https://doi.org/10.2174/0122115501417613251020102808
/content/journals/cbiot/10.2174/0122115501417613251020102808
/content/journals/cbiot/10.2174/0122115501417613251020102808
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  • Article Type:     Research Article
Keywords: DFT and ESP studies ; molecular dynamics studies ; Uropathogenic Escherichia Coli (UPEC) ; in silico ; molecular docking ; Urinary Tract Infections (UTI)

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