Study of the potential of the active compounds of Moringa oleifera leaves in increasing the intake of Fe⁺³ in pregnant women through docking and molecular dynamics methods on the enzyme “Human duodenal cytochrome B” (Dcytb)

Iron supplements in pregnant women are often combined with ascorbic acid. The electron donor ascorbic acid plays an essential role in reducing Fe⁺³ ions to Fe⁺² so that they are easily absorbed through the DMT1 channel of human duodenal enterocyte cells. The electron transfer mechanism of ascorbic acid also allows other compounds rich in hydroxyl groups to play a role, such as compounds belonging to the phenolic-flavonoid group. The Moringa oleifera plant, apart from being known to be rich in nutrients such as ascorbic acid and high concentrations of Fe+3, also contains various secondary metabolites such as compounds belonging to the phenol-flavonoid group, alkaloids, steroids, glucosinolates, and fatty acids. This study attempted to screen 50 bioactive compounds contained in the leaves of the Moringa oleifera plant as reducing agents for Fe+3 to Fe+2 ions through the enzyme of “Human Duodenal Cytochrome B” (Dcytb). The crystal structure (3D) of the Dcytb enzyme was obtained from a web server https://www.rcsb.org/ (Pdb. id 5ZLG). Meanwhile, the 3D structures of 50 compounds from Moringa oleifera were downloaded in “SMILES” format from PubChem and converted to 3D format using the “MOE Builder tool”. The research method used molecular and dynamic molecular docking techniques through “MOE 10. 2008” software. The results of molecular docking of the Dcytb enzyme obtained 19 ligand compounds with stronger ΔG_binding values than the ascorbic acid as control ligands. The strongest affinities were shown by Quercetin-3-O-glucoside with a ΔG_binding value of -23.10 kcal/mol, Kaempferol-3-O-glucoside with a ΔG_binding value of -18.99 kcal/mol, Rutin with a ΔG_binding value -18.07 kcal/mol, Vicenin-2 with a ΔG_binding value of -17.31 kcal/mol, etc. In comparison, Ascorbic acid control has an affinity with a ΔG_binding value of -13.29 kcal/mol. All of the tested phenolic-flavonoid compounds except genistein have a hydroxyl group with a strong affinity for the Dcytb enzyme, interacting in the "pocket" region of the enzyme to form hydrogen bonds with Lys 79, Lys 83, and Arg 152. The results of the molecular dynamics simulation of glucoconringin, kaempferol-3-O-glucoside have a strong interaction and is better stable than ascorbic acid at its binding site, while epicatechin has a stability pattern similar to that of ascorbic acid observed in 2000 pc of molecular dynamics simulations. These characteristics allow Moringa oleifera to be rich in compounds that have the potential to activate the Dcytb enzyme.