Isolation of sesquiterpene coumarins from Ferula assa-foetida using macroporous resin and molecular dynamics

Ferula assa-foetida oleo-gum-resin ( F. assa-foetida , asafoetida) is rich in bioactive sesquiterpene coumarins that exhibit various pharmacological effects, including anticancer, antimicrobial, and anti‑inflammatory activities. The selective isolation of sesquiterpene coumarins and removal of odorous sulfur compounds are essential steps for achieving their direct therapeutic effects. Macroporous adsorption resins represent a cost-effective approach for natural product isolation. In this study, the main sesquiterpene coumarins present in the extract of asafoetida (isosamarcandin and kellerin) were first isolated and purified, and then were used as a standard for designing a method to enrich these compounds in the plant extract using several macroporous resins, including A-740, A-750, A-950, LXA-10, and HP-20. Among them, the non‑polar styrene-divinylbenzene resin HP-20 exhibited the highest affinity. The enrichment factors using HP‑20 were 4.4 for kellerin and 2.6 for isosamarcandin. Among the models tested, the pseudo-second-order (PSO) model provided the best overall fit to the experimental data for both isosamarcandin and kellerin, as indicated by higher R 2 values and closer agreement between calculated and experimental Qe, and the equilibrium behavior was well fitted by the Freundlich isotherm. An 80% aqueous ethanol solution was identified as the optimal desorption solvent, effectively recovering the majority of adsorbed coumarins and eliminating the need for absolute ethanol. The HP-20 resin also demonstrated excellent reusability, during multiple adsorption-desorption cycles without significant performance loss. Furthermore, molecular dynamics simulations revealed that isosamarcandin exhibits stronger interaction energy than kellerin, indicating stronger interactions. The interaction between the sesquiterpene coumarins and the resin is controlled primarily by van der Waals forces, as confirmed by energy comparisons. Overall, the results of this study confirm the efficacy of HP-20 resin as a suitable method for the separation and isolation of sesquiterpene coumarins. This approach provides a practical method for the laboratory-scale preparation of enriched coumarin fractions with potential relevance for pharmacological studies.