In silico analysis of the inhibition of propanediol dehydratase by some active compounds of Curcumna longa: A promising drug-based therapy for managing Crohn's disease

Abstract

Abstract Crohn’s disease (CD) is a complex inflammatory bowel disease with a global impact on healthcare systems. This study explores potential therapeutic strategies against CD, focusing on inhibiting propanediol dehydratase (PduC), an enzyme linked to intestinal inflammation. In silico homology modeling was employed to predict the tertiary structure of PduC, and subsequent molecular docking with 182 phytochemicals from Curcuma longa (CL) was performed. The docking results revealed seven active compounds with superior binding affinities compared to azathioprine, a standard CD treatment. These compounds, including cyclocurcumin, curcumin, and demethoxycurcumin, exhibited strong anti-inflammatory properties through modulation of inflammatory molecules in the body. ADMET evaluation indicated their potential as drug candidates, demonstrating favorable pharmacokinetic properties. Furthermore, the compounds displayed interactions with amino acid residues in PduC’s active site, essential for inhibitory action. The study emphasizes the need for further in vitro, in vivo, and clinical trials to validate CL compounds’ effectiveness against CD. Although the findings provide valuable insights into potential therapeutic targets for CD, more extensive investigations are necessary to confirm the compounds’ inhibitory potential and pave the way for the development of novel drugs for CD management.