Molecular docking analysis of chemical constituents from the stem barks of podocarpus falcatus and evaluation for antibacterial activity

Abstract Chromatographic separation of equal ratio of CH2Cl2-MeOH extract of the stem barks of Podocarpus falcatus led to the isolation of three compounds namely: 4β-carboxy-19-nor-totarol (1), β-sitosterol (2), 4-hydroxybenzoic acid (3) and (E)-methyl-3, 4, 5-trimethylhex-2-enoate (4). The structures of the compounds were established based on the analysis of 1D and 2D NMR spectroscopic data. These compounds were reported from this plant for the first time. The crude extract and isolated compounds were evaluated for their antibacterial activity using disk diffusion assay method. The crude extract showed a strong activity against S. aureus. Compounds (1) and (2) showed a relatively moderate activity against S. flexineri and S. typhimurium respectively, whereas, compound (3) and (4) demonstrated a strong activity against S. aureus. The crude extract and the isolated compounds showed considerable antibacterial activity as compared to the reference gentamycin indicating that this plant has potentially antibacterial properties. Docking studies were performed with S. aureus Gyrase and human DNA topoisomerase IIβ by using AutoDock Vina. ADMET were predicted by Swiss ADME, Pre ADMET. In silico, molecular docking studies of compounds (1-3) showed strong interaction with S. aureus Gyrase with binding energy value ranging from −6.1 to −8.6 kcal/mol, with respect to ciprofloxacin and Doxycycline −8.4 kcal/mol and -13.0 kcal/mol respectively, whereas, analysis against human topoisomerase IIβ with binding energy value ranging from −6.4 to −10.1 kcal/mol, with respect to Vosaroxin and Abiraterone −10.2 and -11.8 kcal/mol respectively. The results obtained suggest that compounds (1-3) are potential S. aureus Gyrase inhibitors and might be used as antibacterial agents and compound (1 and 2) are potential topoisomerase IIβ inhibitors and might be used as anticancer agents. The ADMET studies showed the highest drug-likeness properties for studied compounds (1-3). Compounds (1-3) have no acute toxicity. The studied compounds were predicted to be non- hepatotoxic, non- cytotoxic, non-mutagenic and non-irritant. However, compound (2) is Immunotoxic