Isolation, antibacterial evaluation, molecular docking and DFT studies of two previously unreported terpenoids from the stem bark of Croton zambesicus

The methanolic crude extract of Croton zambesicus stem bark exhibited in vitro antibacterial activity against Staphylococcus aureus SP79 and O74, with MIC values of 62.5 and 78.12 µg/mL, respectively. The subsequent chemical investigation of the extract led to the isolation of two previously unreported terpenoids 1 and 2, along with thirteen known compounds (3 – 15). Compound 1 exhibited significant antibacterial activity against Pseudomonas aeruginosa ATCC 2108 and S. aureus NGTC 12973, with the same MIC value of 8.2 µg/mL. Compound 11 also demonstrated potent activity against S. aureus SP79, P. aeruginosa ATCC 2108, and S. aureus NGTC 12973, with an MIC of 4.1, 8.20 and 8.2 µg/mL, respectively. An in silico molecular docking study was performed in compound 1 using the K4U-bound crystal structure of type II peptide deformylase, an enzyme implicated in S. aureus resistance, particularly to methicillin. Compound 1 showed a favorable binding energy (∆G = −5.22 kcal/mol), which compares well with the native ligand (∆G = −5.22 kcal/mol). Furthermore, compound 1 was subjected to density functional theory (DFT) analysis using the B3LYP functional and the 6–311 + +G(d,p) basis set, revealing a relatively low energy gap (ΔEg = 5.8 eV), indicative of good chemical reactivity and stability.