Phytochemical profiling and antibacterial activities of Ziziphora tenuior root extracts: a molecular docking against VanA of vancomycin-resistant enterococci

Abstract

Medicinal plants, renowned for their antibacterial phytocompounds and secondary metabolites, hold significant promise in addressing antibiotic-resistant bacterial strains. This study aimed to conduct phytochemical profiling of the methanolic and dichloromethane extracts of Ziziphora tenuior root using the GC-MS technique. These extracts' antioxidant potential was assessed via DPPH assay and their antibacterial activity was evaluated against S. aureus, E. coli, and VRE bacterial strains. Furthermore, the drug-ligand interactions between the extracts' biocompounds and d-alanyl-d-lactate ligase (VanA) protein of vancomycin-resistant enterococci strains (VRE) were analyzed using molecular docking. Based on the results, 74% of methanolic extract consisted of (3methyl, 24S)-stigmast-5-en-3-ol (which is a β-sitosterol), followed by Tetrasiloxane, decamethyl (15.5%), and 1-methyl-4-phenyl-5-thioxo-1,2,4-triazolidin-3-one (10.5%). Also, the only predominant compound identified in the dichloromethane extract was Benzo[h]quinoline, 2,4-dimethyl-. Both extracts showed antioxidant activity, while the antioxidant activity of the methanolic extract (IC₅₀ = 95.33 μg/ml) was significantly higher than that of the dichloromethane extract (IC₅₀ = 934.23 μg/ml). Also, both extracts displayed substantial antibacterial efficacy against the tested pathogens, particularly against VRE. Moreover, the in silico analysis revealed that (3methyl, 24S)-stigmast-5-en-3-ol and Benzo[h]quinoline,2,4-dimethyl- exhibited notable interactions with VanA through docking energy values of - 9.0 and - 9.1 kcal/mol, respectively. Furthermore, these compounds formed 2 and 1 hydrogen bonds with VanA, respectively, highlighting their potential as effective interactants. These findings provide valuable visions into the therapeutic potentials of these plant-derived biocompounds in combating antibiotic-resistant bacterial infections.

Keywords: Antibiotic resistance; Plant extract; VanA; Vancomycin.

Fig. 1

The DPPH radical scavenging of methanolic and dichloromethane extracts of Z. tenuior roots

Fig. 2

The 3D structures of VanA protein (a) and (3methyl, 24S)-stigmast-5-en-3-ol (b) and Benzo[h]quinoline, 2,4-dimethyl- (c) biocompounds. Also, (d) and (e) show the docked complexes of VanA-(3methyl, 24S)-stigmast-5-en-3-ol, and VanA-Benzo[h]quinoline, 2,4-dimethyl-, respectively. Ligands are depicted in brown rods; residues are represented as blue rods; and hydrogen bonds are illustrated as blue lines