Introduction::
Inflammatory Bowel Disease (IBD) encompasses a group of chronic disorders
distinguished by inflammation of the gastrointestinal tract. Among these, Crohn's Disease
(CD) stands out as a complex and impactful condition due to challenges for both diagnosis and
management, making it a cynosure of research.
Method::
In CD, there is the predominance of proinflammatory bacteria, including the Adherentinvasive
Escherichia coli (AIEC) with virulence-associated metabolic enzyme Propanediol Dehydratase
(pduC), which has been identified as a therapeutic target for the management of CD. Herein,
molecular modeling techniques, including molecular docking, Molecular Mechanics with Generalized
Born and Surface Area (MMGBSA), drug-likeness, and pharmacokinetics profiling, were
utilized to probe the potentials of eighty antibacterial compounds to serve as inhibitors of pduC.
Result::
The results of this study led to the identification of five compounds with promising potentials;
the results of the molecular docking simulation revealed the compounds as possessing better
binding affinities for the target compared to the standard drug (sulfasalazine), while Lipinski’s rule
of five-based assessment of their drug-likeness properties revealed them as potential oral drugs.
MMGBSA free energy calculation and Molecular Dynamics (MD) simulation of the complexes
formed a sequel to molecular docking, revealing the compounds as stable binders in the active site
of the protein.
Conclusion::
Ultimately, the results of this study have revealed five compounds to possess the potential
to serve as inhibitors of pduC of AIEC. However, experimental studies are still needed to
validate the findings of this study.