Potential MAO‐B Inhibitors from Cissampelos capensis L.f.: ADMET, Molecular Docking, Dynamics, and DFT Insights

This study explores the therapeutic potential of three proaporphine alkaloids—cissamaline, cissamanine, and cissamdine, which were recently isolated from Cissampelos capensis L.f., against Parkinson's disease (PD). Using computational techniques, we investigated their efficacy as inhibitors of a key protein in PD. ADMET analysis demonstrated that these alkaloids conform to the Lipinski, Pfizer, Golden Triangle, and GSK rules, indicating favorable safety, oral bioavailability, and a high probability of passing the human intestinal and blood‐brain barriers. They were neither substrates nor inhibitors of any CYP enzymes tested, indicating minimal metabolic interference and an enhanced safety profile. Molecular docking studies revealed strong binding energies with MAO‐B, PD's target. MD simulations supported these findings, showing stable interactions with MAO‐B, while Density Functional Theory (DFT) calculations highlighted the electrophilic nature of cissamanine, enhancing its potential as an effective inhibitor. These results advocate further in vitro and in vivo studies to evaluate their potential as PD therapeutics.