Probing marine macroalgal phlorotannins as an antibacterial candidate against Salmonella typhi: Molecular docking and dynamics simulation approach

The increasing prevalence of drug-resistant bacterial strains, including multidrug-resistant Salmonella typhi, has raised significant concerns about the effectiveness of traditional antimicrobial treatments. To address this issue, the study employed computational techniques to evaluate the potential of natural phlorotannins derived from marine algae as alternative antibacterial agents against S. typhi. A total of 104 phlorotannins were retrieved from PubChem and subjected to molecular docking with three specific target proteins of S. typhi. Among the compounds tested, Compound-10 a derivative of dieckol exhibited the highest affinity for the Omptin family outer membrane protease [pgtE] protein and for the cell invasion protein sipB protein. The docking results revealed strong interactions between the phlorotannins and the target proteins, indicating their potential as antimicrobial agents. Additionally, pharmacokinetic studies using the QikProp module demonstrated that the top-ranked compounds showed favourable drug-like properties with good druggable efficiency, moderate gut-blood barrier transport, and high human oral absorption. Most compounds passed the rule of three and five drug-likeness criteria, indicating their potential as drug candidates. Furthermore, MM-GBSA analysis provided relative binding affinity estimations, ranking the compounds based on their calculated binding energies. These results align reasonably well with experimental binding affinities, reinforcing the potential of the identified compounds as potent binders to their target proteins. This study highlights the promising antibacterial potential of marine phlorotannins against S. typhi. Further in vitro studies are warranted to validate these compounds' efficacy and anti-microbial activity, ultimately paving the way for developing new therapeutic strategies to combat drug-resistant Salmonella infections.