Sesquiterpene Coumarins from Ferula narthex 15-LOX, α-Glucosidase Inhibition and Molecular Docking Studies

Abstract

Ferula narthex Boiss., Apiaceae, is commonly used in Pakistan and India as spice and it is associated with diverse biological activities including antidiabetic and anti-inflammatory. Research has suggested that the genus Ferula is rich in sesquiterpene coumarins. During this project, both in vitro and in silico models were adopted to investigate its traditional use. Based on structural diversity, selected compounds isolated from the exudate were processed for molecular docking studies. The negative binding energies and close proximity to residues in the binding pocket of selected targets including human α-glucosidase (PDB ID 3TOP) and soybean LOX (PDB ID 1IK3) were recorded, which indicated high affinity and tight binding capacity of 10′-R-acetyl-karatavacinol and 10′-R-karatavacinol towards the active sites of α-glucosidase and 15-lipoxygenase. 10′-R-acetyl-karatavacinol exhibited the highest inhibition of α-glucosidase in vitro (IC50 0.05 mM), whereas in the 15-lipoxygenase inhibition assay, 10′-R-karatavacinol was most active (70%, at 0.023 mM final concentration). It was therefore concluded that 10′-R-acetyl-karatavacinol had the highest α-glucosidase inhibitory activity, whereas 10′-R-karatavacinol was a 15-lipoxygenase inhibitor with potentially anti-inflammatory properties.