Phytochemical characterization and Antibacterial Efficacy of Two Essential Oils: GC-MS Profiling, In Vitro Antibacterial Testing, and In Silico ADMET, Molecular Docking, and Molecular Dynamics Simulation

Abstract

Medicinal plants serve as a prolific source of bioactive compounds with diverse biological activities, positioning them as a pivotal focus in research related to alternative medicine and pharmacology. This study investigates the phytochemical composition and antibacterial potential of essential oils derived from Cotula cinerea and Origanum Majorana L., two medicinal plants native to the El Oued region of Algeria and traditionally used in folk remedies for various ailments. The essential oils exhibited promising antibacterial properties, distinguished by their unique chemical profiles and notable efficacy. Using hydrodistillation, the extraction yield of Origanum Majorana L. oil reached 1.45%, compared to 0.90% for Cotula cinerea, with variations influenced by geographical factors such as soil composition and climate. Gas Chromatography-Mass Spectrometry (GC/MS) analysis identified trans-thujone as the predominant compound, accounting for 51.86% of Cotula cinerea oil and 33.3% of Origanum Majorana L. oil, along with santolina triene (16.4%) in the latter. These results underscore notable chemical differences compared to prior studies conducted in other regions. In biological assays, Origanum Majorana L. oil demonstrated superior antibacterial activity, achieving a 25.6 mm inhibition zone against S. aureus, significantly outperforming amoxicillin, which exhibited a mere 0.1 mm zone. Furthermore, IC₅₀ values highlighted the oils' potency, with Origanum Majorana L. displaying an IC₅₀ of 1.5 mg/mL against E. coli, compared to 3.96 mg/mL for amoxicillin. Computational studies corroborated the experimental findings. Molecular docking revealed that trans-thujone interacts strongly with bacterial protein active sites, particularly binding to HIS299 and ASP197 residues in E. coli, with a binding energy of -9.5 kcal/mol, indicating its potential to disrupt bacterial functions. Molecular Dynamics Simulations (MDS) further validated the stability of this interaction over a 100-nanosecond period, characterized by minimal atomic fluctuations (RMSD < 2 Å), reinforcing its candidacy as a potential therapeutic agent. Regarding pharmacological safety, ADMET predictions indicated low toxicity for the principal compounds (classified under Toxicity Class 5) and favorable blood-brain barrier (BBB) permeability, without susceptibility to P-glycoprotein (P-gp) efflux. Nevertheless, compounds such as cis-Verbenyl acetate demonstrated inhibition of the CYP2C9 enzyme, suggesting the need for further investigation into possible drug interactions.