New Halogenated Compounds from Seaweed with Potential Inhibitory Activity against Malaria.

Malaria is one of the most important infectious diseases worldwide. The causative of the most severe forms of malaria, , has developed resistances against all the available antimalarial drugs. In the present study, the phytochemical investigation of the green seaweed has afforded two new compounds -, along with 4 known ones -. The structures of the compounds had been confirmed using 1& 2D-NMR and HRESIMS analyses. Extensive machine-learning-supported virtual-screening suggested cytochrome-C enzyme as a potential target for compound . Docking, absolute-binding-free-energy (Δ) and molecular-dynamics-simulation (MDS) of compound revealed the strong binding interaction of this compound with cytochrome-C. In vitro testing for crude extract and isolated compounds revealed the potential in vitro inhibitory activity of both extract and compound against . The crude extract was able to inhibit the parasite growth with an IC value of 1.8 ± 0.35 µg/mL. Compound also showed good inhibitory activity with an IC value of 3.2 ± 0.23 µg/mL. Meanwhile, compound showed moderate inhibitory activity with an IC value of 19.3 ± 0.51 µg/mL. Accordingly, the scaffold of compound can be considered as a good lead compound for the future development of new antimalarial agents.