Total synthesis of (±)-Glabridin with molecular docking and biological evaluation

The bioactive isoflavan glabridin of Glycyrrhiza glabra remains in the limelight because of its widespread pharmacological prospect. Here, a better and eco-friendly synthetic method to (±)-glabridin has been introduced, that relies on a six-step protocol, and that is more overall yielding, less dependent on chromatographic purification, and more operationally simpler than previously described and patented ones. The synthesized (±)-glabridin is very effective antioxidant, showing 87.46% the percentage of inhibition. Antibacterial assay indicates that there is a distinct strain-dependent reaction, with a significant response against Escherichia coli (MIC = 33.8 μM) and moderate efficacy against Staphylococcus aureus (MIC = 125 μM). Cytotoxicity assay and IC50 values show a dose-response profile, (±)-glabridin would not be cytotoxic until 62.5 μM and therefore, these concentrations would be more applicable to mechanistic or efficacy research which would need minimal viability decline and a good safety margin within the assayed concentration range. In addition, molecular docking experiments have been performed against the chosen biological targets, which are in agreement with the experimental findings. On the whole, this study holds a viable and green chemistry principles guided synthesis of (±)-glabridin that indicates how it could be used in multidrug functions and pertains to the future bioorganic and medicinal chemistry research.