Glucosinolates and Indole-3-carbinol from Brassica oleracea L. as inhibitors of E. coli CdtB: insights from molecular docking, dynamics, DFT and in vitro assay.

Escherichia coli (E. coli), a common human gut bacterium, is generally harmless but capable of causing infections and contributing to diseases like urinary tract infections, sepsis/meningitis, or diarrheal diseases. Notably, E. coli is implicated in developing gallbladder cancer (GBC) either through ascending infection from the gastrointestinal tract or via hematogenous spread. Certain E. coli strains are known to produce toxins, such as cytolethal distending toxins (CDTs), that directly contribute to the genetic mutations and cellular abnormalities observed in GBC. Broccoli (Brassica oleracea) is known for its health-promoting properties, including antimicrobial, antioxidant, and immunomodulatory effects, and is rich in essential compounds. Our study investigates the potential of the phytochemicals of B. oleracea to inhibit the CdtB (PDB ID: 2F1N) protein of E. coli which plays a significant role in the pathogenesis of GBC. By employing in silico molecular docking, Glucosinolates and Indole-3-carbinol emerged as promising inhibitors, demonstrating strong bonding affinities of -8.95 and - 8.5 Kcal/mol, respectively. The molecular dynamic simulation showed that both compounds maintained stable interaction with CdtB with minimal conformational changes observed in the protein-ligand complexes. Additionally, the ADMET analysis provided evidence for the drug-likeness properties of the lead compounds. Furthermore, the DFT (Density Functional Theory) revealed that Indole-3-carbinol is more chemically stable but less reactive than Glucosinolates, with HOMO-LUMO gaps of 5.14 eV and 4.50 eV, respectively. Finally, the in vitro antibacterial assessment confirmed the inhibitory effect of Glucosinolates and Indole-3-carbinol against E. coli through disc diffusion assay with the zone of inhibition 34.25 ± 0.541 and 28.67 ± 0.376 mm compared to the control ciprofloxacin. Our study provides crucial data for developing novel therapeutic agents targeting E. coli-associated GBC from the phytochemicals of B. oleracea.

Supplementary information: The online version contains supplementary material available at 10.1007/s40203-024-00276-3.