Sargassum incisifolium and Ulva spp metabolites activity and their molecular dynamics simulation against Fusarium oxysporum 14-alpha-demethylase

Abstract

Fusarium oxysporum, a major agricultural pathogen, poses severe risks to crops worldwide. With increasing resistance to conventional antifungal agents, there is an urgent need for alternative treatments. Seaweeds such as Ulva spp. and Sargassum incisifolium are promising sources of bioactive compounds that may offer novel antifungal properties. This study investigates the antifungal activity of acetone extracts from Ulva spp. and Sargassum incisifolium against F. oxysporum, with the goal of identifying specific bioactive compounds responsible for this activity and evaluating their effectiveness quantitatively. We prepared acetone extracts from both seaweed species and assessed their antifungal activity using a series of in vitro assays. The total phenolic content (TPC) and antioxidant capacity were determined for each extract. LC-qTOF-MS/MS was employed for phytochemical profiling, while molecular docking and molecular dynamics simulations were used to predict interactions between identified compounds and the 14-alpha-demethylase enzyme of F. oxysporum. The TPC was 2.72±0.009 and 2.23±0.009 GAE/mg dry weight for Ulva spp and S. incisifolium. Additionally, significant antioxidant activity was observed, with IC50 values of 8.38±0.06 µg/mL for Ulva spp and 8.01±0.07 µg/mL for S. incisifolium, which are comparable to ascorbic acid (5.23±0.04 µg/mL). Phytochemical analysis revealed high levels of terpenoids, phenolics, and fatty acids. In molecular docking, compounds such as medicocarpin, corynanthine, and merulinic acid demonstrated strong binding affinities (binding energies ≤ -7.5 kcal/mol). Molecular dynamics simulations confirmed stable interactions over 100 ns, with medicocarpin exhibiting the most stable binding profile. The study demonstrates that acetone extracts of Ulva spp. and S. incisifolium possess significant antifungal activity against F. oxysporum. Medicocarpin, in particular, emerged as a promising candidate for further development as an antifungal agent. These findings underscore the potential of seaweed-derived compounds as antifungal agents against fungal pathogens and highlight the need for further investigation into their practical applications in plant disease management. Specifically, Medicocarpin emerged as a promising in silico candidate, warranting further experimental validation.