Isocostic Acid, a Promising Bioactive Agent from the Essential Oil of Inula viscosa (L.) Insights from Drug Likeness Properties, Molecular Docking and SAR Analysis
Résumé
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. © 2019 Wiley-VHCA AG, Zurich, Switzerland