Theoretical visualization of covalent and non-covalent interactions: molecular diversity and substituent effects governing the reactivity of Bulbophyllum bibenzyl derivatives

Muscatilin and Gigantol are predicted to have promising activity-safety profiles as potential antioxidant lead compounds.

• Frontier molecular orbital analysis indicated larger HOMO-LUMO gaps (5.41-5.67 eV) for the derivatives compared to 3.97 eV for reference compounds, suggesting higher electronic stability.
• Muscatilin showed the lowest hardness (2.70 eV) and highest softness (0.185 eV), which may enhance its chemical reactivity.
• Real-space topological analyses suggested that Muscatilin has a favorable electron density distribution, potentially aiding in radical stabilization through hydrogen or electron transfer.
• SwissADME profiling indicated high gastrointestinal absorption and blood-brain barrier permeability for all compounds except Quercetin, while also predicting high toxicity for Tristin, Muscatilin, and Gigantol (2260 mg/kg).
• Molecular docking revealed binding affinities between -7.2 and -9.2 kcal/mol toward bovine superoxide dismutase, with Muscatilin showing the strongest interaction.
• Molecular dynamics simulations suggested stable ligand binding within the SOD active channel, supported by binding energy estimates.

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