The root essential oil from the Tunisian endemic plant Ferula tunetana: Chemical composition, biological evaluation, molecular docking analysis and drug-likeness prediction

Oxidative stress is closely related to cancer aspects, such as the induction of gene mutations resulting from cellular injury and the effects on transcription and signal transduction factors. In addition, antibiotic resistance is also linked with oxidative stress, which could contribute to the selection of resistant bacterial strains. With this in mind, and considering that essential oils are well known to display antioxidant, antimicrobial, and cytotoxic activities, this study was destined to investigate the chemical composition and to screen these properties for the root essential oil (REO) of the Tunisian endemic species Ferula tunetana Pomel ex Batt. The REO GC/MS analysis led to the identification of nine compounds, representing 94.5% of the total oil composition. The phytochemical profile of this essential oil (EO) was characterized by the dominance of sesquiterpenes, comprising 11.7% of sesquiterpene hydrocarbons and 82.8% of oxygenated sesquiterpenes. The three major constituents of the EO were caryophyllene oxide (33.9%), α-cyperone (13.9%), and 14-hydroxy-9-epi-(E)-caryophyllene (12.3%). REO showed a good antioxidant potential against DPPH (IC₅₀ = 30.13 ± 0.28 μg/mL), O₂^•- (IC₅₀ = 42.87 ± 0.81 μg/mL) and H₂O₂ (IC₅₀ = 48.03 ± 1.21 μg/mL). Additionally, the antimicrobial activity results showed that REO had a strong antibacterial potential against all target microbial strains, including five Gram-negative, six Gram-positive bacteria, and two Candida species (MICs = 0.039–0.625 mg/mL). Furthermore, the extracted EO was found to have good cytotoxic properties against five human cell lines viz. HT-29, HCT-116, HeLa, A549 and U937, with IC₅₀ values ranging from 3.37 ± 0.02 to 46.66 ± 1.22 μg/mL. The main REO constituents were docked to the human DNA topoisomerase IIα enzyme and the in vitro cellular toxicities were rationalized. The drug-likeness of the main compounds identified in the studied EO was predicted. Overall, the results of the current study prove that the EO of F. tunetana roots has a noteworthy antioxidant potential and represents an interesting candidate to treat infectious diseases and cancer.