Structural prediction and mass-guided isolation of new potentially bioactive compounds from ammoniacum (Ferula communis)

The recent proliferation and prevalence of antimicrobial multi-resistant infections has prompted the development of other strategies and alternatives to urgently combat this global threat. For this purpose, past mastering of remedies formulation appears as a wealth of resources for present research. In particular, Arab Medieval Pharmacopeias (AMP) were explored by our interdisciplinary team gathering researchers from biology, chemistry, humanities and informatics sciences. One remedy from the Ibn Al-Kindi Pharmacopeia (9th Century) which combines plant-based products and metal was reproduced and biological activity was tested. Ammoniacum, one of the five ingredients, showed antimicrobial activity against Gram-positive cutaneous bacteria. This present study aimed to further explore this gum-resin from Ferula communis using a molecular-networking-guided method for the accelerated discovery of new compounds. HPLC-PDA-HRMS/MS molecular-networking-based dereplication strategy highlighted the presence of known sesquiterpene coumarins (SC) among potential new derivatives by comparison of their MS/MS fragmentation spectra. By this approach, a new hydroxycinnamic-ferulenol (1) ([Fig. 1]) derivative was predicted in the extract. Mass-guided isolation followed by structural characterisation allowed us to corroborate the predicted structure of this new SC compound. This targeted isolation led to a total of two known SC exhibiting antimicrobial activity (2, 3) and two new SC structures (1, 4). The results of the present study confirm the interest attached to Ferula communis’ gum exploration in the discovery of new structures not described yet.

Fig. 1 Structures of compounds 1-4.

Publication History

Article published online:
16 November 2023