Desalegn Abebe Deresa*, Zelalem Abdissa, Getahun Tadesse Gurmessa and Negera Abdissa
Chromatographic separation of an equal ratio of CH2Cl2-MeOH extract of the stem barks of Podocarpus falcatus led to the isolation of three compounds 1-3. The structures of the compounds were established based on the analysis of 1D and 2D NMR spectroscopic data. Compound 3 was reported from this plant for the first time. The crude extract and isolated compounds were tested for their antibacterial activity using the disk diffusion assay method against five bacteria strains. The crude extract showed strong activity against S. aureus. Compounds 1 and 2 showed relatively moderate activity against S. flexineri and S. typhimurium respectively, whereas, compound 3 demonstrated strong activity against S. aureus. Docking studies were performed against S. aureus Gyrase and human DNA topoisomerase IIβ by using AutoDock Vina. ADMET was predicted by SwissADME, PreADMET. In-silico molecular docking studies of compounds 1-3 showed strong interaction with S. aureus Gyrase with binding energy values ranging from −6.1 kcal/mol to −8.6 kcal/mol, concerning 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 kcal/mol to -10.1 kcal/mol, for Vosaroxin and Abiraterone -10.2 kcal/mol 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 compounds 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, noncytotoxic, non-mutagenic, and non-irritant. However, compound 2 is immunotoxic. The results of antibacterial activity and molecular docking suggested that this plant has potentially lead compounds for drug discovery.