Xeroderris stuhlmannii is a plant that has been used for a long time in Cameroon and in Africa for the treatment of various diseases including: digestives disorders, diabetes, hypertension and skin infections. Four isolated compounds from the leaves’ crude extract were chosen based on their antimicrobial activity reported in our previous work against Escherichia coli, Staphylococcus aureus, Klebsiella pneumonae and Candida albicans. Materials and Methods: Molecular docking calculations were made by AutoDock Vina software and the docking studies were performed with the same strains, while ADMET values were predicted by QikProp. 3D and 2D interaction with bacterial and fungal complexes are shown. Results: Based on the overall observations, we noticed that compounds bearing prenyl or geranyl groups at the C-7 or C-4’ position exhibited high docking scores and interactions than those lacking such substituents. Undeniably, these substituents are decisive contributor to CYP51 inhibition, which promotes strong hydrophobic occupation of the active site and then facilitating interaction with the heme group. WF54 scaffold fits the hydrophobic pocket of DHFR, accounting for its potent antibacterial effect, while the isoflavone skeleton of NKL8 is structurally aligned with the geometry of DNA gyrase ATP binding pocket, which enables it to form a vast network of hydrogen and electrostatic bonds that disrupts ATP hydrolysis.
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