Isocostic Acid, a Promising Bioactive Agent from the Essential Oil of Inula viscosa (L.): Insights from Drug Likeness Properties, Molecular Docking and SAR Analysis

Abstract The chemical composition of the essential oil (LEO) and its volatile fractions (V 1 –V 10 ) collected during the hydrodistillation process every 15 min from the fresh leaves of I. viscosa (L.), growing in Tunisia, were analyzed by GC‐FID and GC/MS. Eighty‐two compounds, representing 90.9–99.4 % of the total samples, were identified. The crude essential oil (LEO) and its fractions (V 1 –V 10 ) were characterized by the presence of a high amount of oxygenated sesquiterpenes (82.7–95.8 %). Isocostic acid ( 1 ) was found to be the most abundant component (37.4–83.9 %) and was isolated from the same essential oil over silica gel column chromatography and identified by spectroscopic methods ( 1 H, 13 C, DEPT 135 NMR and EI‐MS) and by comparison with literature data. Furthermore, the fresh leaves essential oil (LEO), its volatile fractions (V 1 –V 10 ) as well as compound 1 were screened for their antibacterial, antityrosinase, anticholinesterase and anti‐5‐lipoxygenase activities. It was found that the isolated compound 1 exhibited an interesting antibacterial activity against Staphylococcus aureus ATCC 25923 (MIC=32 μg/mL) and Enterococcus faecalis ATCC 29212 (MIC=32 μg/mL) and the highest antityrosinase activity (IC 50 =13.82±0.87 μg/mL). Compound 1 was also found to be able to strongly inhibit 5‐lipoxygenase with an IC 50 value of 59.21±0.85 μg/mL. The bioactivity and drug likeness scores of compound 1 were calculated using Molinspiration software and interpreted, and the structure‐activity relationship (SAR) was discussed with the help of molecular docking analysis.