Abstract
Background: Salmonella typhimurium is a pathogen, causing a threat to human health worldwide. The severity in treatment raises as the pathogen develops resistance against wellestablished drugs. To combat these multidrug-resistant pathogens, novel target and antimicrobial agents are needed. The literature supports the potency of L-asparaginase as a novel target as it provides survival benefit to the pathogen. The plant-derived molecules holds remarkable potential and therefore, their antimicrobial properties are explored in the present study.
Methods: In the present work in silico studies were performed to test the efficacy of chemoconstituents of spices as antimicrobial agents against the novel target l-asparaginase. The pharmacokinetic profile of the lead molecules were also studied by determining their ADMET properties.
Results: The results obtained through in silico studies suggest the efficacy of 27 ligands (spices chemoconstituents) as anti-microbial agents that were effective in blocking the virulent protein lasparaginase. The lowest docking score obtained for piperic acid derivative 1 was -7.591 while for ampicillin (the standard drug) was -5.797. Piperic acid derivative 2, drupanin, ent-copalic acid, 4- amino cinnamic acid, 3-O-prenyl coumaric acid also displayed good results in terms of docking score and ADMET profiling. The amino acid residues commonly involved in the interaction within the druggable pockets are Thr35, Thr55, Thr115, Gly34, Gly83, Asp116.
Conclusion: The molecular docking and ADMET profiling of spices chemoconstituents pave the path for future drug development against the multidrug resistant S. typhimurium via L-asparaginase targeting.
Keywords: Salmonella typhimurium, L-asparaginase, natural ligands, molecular docking, antimicrobial, chemoconstituents.
Graphical Abstract
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