Endophytic Aspergillus sp. from Phragmites australis: A source of DNA gyrase inhibitors with antibiofilm, antioxidant, and cytotoxic potentials: in vitro supported by in silico

Abstract

A fungal isolate, AHMSH2, was obtained from Phragmites australis collected in El-Beheira, Egypt, and identified as Aspergillus sp. via 18S rRNA gene sequencing (GenBank: PQ432869.1). Large-scale fermentation on potato dextrose broth followed by GC-MS profiling revealed 49 metabolites, with canthaxanthin as a dominant compound. Crude extracts exhibited selective antimicrobial activity, with moderate inhibition against Escherichia coli and limited effects on other pathogens. Notably, antibiofilm assays exhibited a marked suppressive effect on Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. Antioxidant screening via DPPH radical scavenging yielded a maximum inhibition of 43.01 %. DNA Gyrase-B inhibition assays confirmed a potent IC₅₀ of 5.23 μg/mL, while molecular docking of canthaxanthin indicated a stable binding affinity of −8.1 kcal/mol with essential interactions at the ATP-binding pocket. Additional docking against OMPX (1QJ8) highlighted hydrophobic and hydrogen bond contributions. In vitro, cytotoxicity showed selective effects on UO-31 renal cancer cells (IC₅₀ = 26.58 μg/mL). ADME and toxicity profiling revealed favorable intestinal absorption and metabolic stability, though lipophilicity and CYP3A4 interaction warrant formulation adjustment. The extract's multi-target potential highlights Aspergillus sp. AHMSH2 is a promising source of pharmacologically active metabolites.