Bio-active components of Cymbopogon martinii essential oil as therapeutics targeting bacterial Penicillin-Binding-Proteins (PBPs): Aroma profile, in silico-docking, pharmacokinetics, and wet-lab validation

Abstract

Cymbopogon martinii, also known as Palmarosa, is an underutilized plant in the tropical region. Due to its outstanding antioxidant potential, it has been used as a part of conventional medicine and beauty product. The objective of the present study was aromatic profiling of Palmarosa essential oil and molecular docking of Palmarosa essential oil bioactive components (Geraniol, Geranial, Linalool, Fenchyl alcohol, 6-methylhept-5-en-2-one, Borneol, Elemol, δ-cadinol) against six bacterial Penicillin-binding Proteins (PBP1a, PBP2a, PBP3, PBP4, PBP5, and PBP 6) and in-vitro support. GC-FID was used to find out aromatic profiling. For docking Cb-dock2 tool was used. Ligand-Protein 3D interactions were also studied. In-silico ADMET pharmacoinformatics aspects (Physicochemical, Lipophilicity, Medicinal Chemistry, Druglikeness, Absorption, Water Solubility, Distribution, Metabolism, Pharmacokinetics, Excretion, Environmental Toxicity, Tox21 Pathway and Toxicophore Rules) with PASS prediction of all the ligands have been bio-prospected. Wet lab validation was performed by Gram-positive and Gram-negative bacterial strains. GC-FID profiling revealed the presence of various major and minor components. Docking analysis indicated effective binding of all the ligands with all the six PBPs (PBP1a, PBP2a, PBP3, PBP4, PBP5, and PBP 6). The interaction results indicate that the PBP-Ligand complexes form hydrogen and hydrophobic interactions. in-silico ADMET study revealed that all the ligand molecules have no toxic effect and good absorption as well. Wet lab validation was performed by Gram-positive and Gram-negative bacterial strains. In-vitro results revealed that the Palmarosa oil was able to inhibit the growth of the bacterial strains thus signifying its role as a potent anti-bacterial drug. These ligands can be used as a basic structure, and various structural modifications can ultimately yield stronger molecules. The Palmarosa essential oil could be a promising antibacterial agent against various strains.

Keywords

• penicillin binding protein
• gc-fid
• admet
• cymbopogon martinii
• geraniol
• in-silico studies