Molecular docking, dynamics simulations, and ADMET evaluation of some indole alkaloids and phenolic compounds from Campylospermum genus (Ochnaceae) as potential antiplasmodial and antimicrobial agents

The increasing resistance of Plasmodium species and pathogenic bacteria to standard treatments highlights the need for the identification of new bioactive agents. Plants belonging to the genus Campylospermum (Ochnaceae), widely utilised in African traditional medicine, are a potential source of secondary metabolites known for their antimicrobial and antiplasmodial activities. This research utilised an integrated in silico methodology to examine the efficacy of seven natural compounds, serotobenine, decursivine, calanthumindole, flavumindole, amentoflavone, sequoiaflavone, and podoscarpusflavone B, previously extracted from Campylospermum species. Molecular docking was conducted against β -lactamase (PDB: 6H2K) and a Plasmodium falciparum enzyme (PDB: 4QNS) utilising MOE software, accompanied by stringent redocking validation (RMSD: 1.28–1.43 Å, both below the 2.0 Å threshold). Binding affinities, interaction patterns, and potential mechanisms were analysed in comparison to the reference inhibitors relebactam and artemisinin. ADMET profiling, encompassing toxicity prediction via ProTox-II, was performed to evaluate drug-likeness and developability. Podoscarpusflavone B demonstrated the highest computed binding affinity for both β -lactamase (− 7.90 kcal/mol) and the Plasmodium enzyme (− 7.63 kcal/mol), establishing five hydrogen bonds and numerous hydrophobic interactions with critical active-site residues. The values indicated improvements ranging from 1.43 to 1.60 times compared to reference inhibitors (relebactam: -5.51 kcal/mol; artemisinin: −4.77 kcal/mol; p < 0.001, ANOVA). Amentoflavone (− 7.65 kcal/mol, − 6.07 kcal/mol) and sequoiaflavone (− 7.25 kcal/mol, − 6.97 kcal/mol) exhibited favourable docking scores and stable interaction profiles (RMSD: 0.77–1.79 Å). The four indole alkaloids exhibited favourable predictions for oral bioavailability, adhered fully to Lipinski’s rule (0 violations), and showed no predicted toxicity across five endpoints (hepatotoxicity, carcinogenicity, immunotoxicity, mutagenicity, cytotoxicity), with LD 50 values ranging from 800 to 1200 mg/kg (Toxicity Class 4). The biflavonoids demonstrated absorption limitations related to molecular size and polarity, with amentoflavone and sequoiaflavone predicted to exhibit hepatotoxicity, immunotoxicity, and cytotoxicity (LD 50 : 150–200 mg/kg, Class 3). An integrated prioritisation matrix that incorporates docking scores, ADME properties, and toxicity profiles has identified podoscarpusflavone B (total score: 11/18), serotobenine (16/18), and decursivine (16/18) as the top candidates for experimental validation. This computational study presents molecular-level hypotheses that may elucidate the ethnopharmacological applications of Campylospermum species. Molecular dynamics simulations were also in support of these results, as it was observed that ligand-bound β-lactamase systems were in a stable conformation after initial equilibration, with lower residue fluctuations compared to the free protein. The presence of key interactions, such as long-lived salt bridges (ASP122-ARG126 and ASP247-ARG222), demonstrates the structural stability and binding affinity of the complexes. The findings highlight the importance of integrated in silico methods for prioritising natural products, while also stressing the necessity of experimental validation via enzyme inhibition assays, antimicrobial susceptibility testing, and toxicity profiling prior to drawing any therapeutic conclusions.