Experimental and In Silico Studies to Unravel the Antioxidant and Antibacterial Properties of Lichen Metabolites from Pseudocyphellaria compar and Pseudocyphellaria nudata

Lichens are a source of diverse compounds with a wide range of biological activities, making them of significant interest for novel drug development. In this study, metabolites were extracted from <i>Lobariaceae</i> lichens, and their antioxidant and antibacterial properties were experimentally investigated and explained using various computational approaches. Specifically, four lichen metabolites were analyzed using three methods to assess their antioxidant capacity. Antibacterial activity assays were conducted against four pathogens, and the minimum inhibitory concentrations (MICs) of the most promising compounds were determined. Ab initio studies were performed to evaluate radical stability. A pharmacological target responsible for the antibacterial effect was identified, and possible binding sites and modes were studied in silico. Metabolite <b>IX</b>, physciosporin, exhibited the highest antioxidant activity, which was associated with the theoretical stability of the radical. Additionally, <b>IX</b> exhibited an MIC of 0.97 μg/mL against <i>S. pyogenes</i>, surpassing the potency of streptomycin. The RecA protein was identified as a potential target, and a possible binding site and pattern of interactions at that site were described. Finally, <b>IX</b> showed low cytotoxicity in human cancer cell lines and was predicted to have favorable oral absorption properties, supporting its potential as a promising antioxidant and antibacterial agent against <i>S. pyogenes.</i>