Targeted isolation of new antibacterial sesquiterpene coumarins from ammoniacum (Ferula communis L.)

Abstract

The use of plant-based remedies in traditional medecine to combat bacterial infections has been scientifically studied. As part of an ongoing research for the discovery of new therapeutic options to treat bacterial infections, Ammoniacum gum resin from Ferula communis L. roots was explored. Ammoniacum appeared in many traditional formulations of Arab, Indian and Western medicines and its use has been reported throughout the centuries. This present study aimed to further explore this gum-resin using a molecular-networking-guided method for the accelerated discovery of new antibacterial compounds. HPLC-PDA-HRMS/MS molecular-networking-based dereplication strategy highlighted the presence of known sesquiterpene coumarins among potential new derivatives. By comparison of MS/MS fragmentation spectra between known and unknown compounds, a hydroxycinnamic sesquiterpene coumarin structure was predicted as a potential new compound. Mass-guided isolation followed by structural elucidation allowed us to corroborate the predicted structure of this new derivative identified as o-coumaric-ω-hydroxyferulenol (10). The new derivative showed MIC₉₀ values of 1.84–6.17 μM against cutaneous Gram-positive bacteria with a bactericidal effect measured by MBC/MCI ratio evaluation and flow cytometry methodology. Furthermore, the new compound showed no in vitro cytotoxicity against eukaryotic cells. This study confirms the interest to analyse with modern techniques ancient traditional remedies in the exploration of new bioactive compounds with therapeutical potential.