Molecular docking and bioactive compounds from endophytic Aspergillus flavus: A pathway to new therapeutics

Abstract

Endophytic fungi are found within internal plant tissues and provide a range of advantages to their hosts. However, the diversity of fungal interactions with medicinal plants remains underexplored. This investigation aimed to isolate and identify endophytic fungi from surface-sterilized leaves of Roscoea purpurea, a medicinal herb known for its therapeutic value. The isolated fungus was identified as Aspergillus flavus through morphological observation, molecular characterization (18S rRNA), and phylogenetic analysis. Ethyl acetate extracts of the fungal culture were analyzed using GC-MS, revealing several bioactive compounds, with Diethyl Phthalate (DEP) as the predominant constituent (82.02 %). The extract exhibited significant biological activities, including cytotoxicity (NRU assay), antioxidant potential (DPPH assay), and antibacterial efficacy. Notably, it showed strong antibacterial activity against Staphylococcus aureus (36.65 ± 1.48 mm) and Bacillus cereus (30.05 ± 0.91 mm), along with moderate anticancer activity against MCF-7 breast cancer cells (IC₅₀ = 348.93 µg/mL). Molecular docking of DEP with key bacterial proteins such as PBP4, α-hemolysin, OmpF, and GyraseA demonstrated moderate to strong binding affinities (−6.7 to −5.4 kcal/mol), suggesting possible mechanisms of antimicrobial action. ADME and drug-likeness assessments using SwissADME and ProTox-II indicated high gastrointestinal absorption, blood-brain barrier permeability, no PAINS alerts, and compliance with Lipinski’s rule of five, supporting its potential as a drug-like compound. Molecular dynamics simulations further validated the stability of protein-ligand interactions. These findings underscore the therapeutic promise of DEP as a bioactive fungal metabolite with dual antibacterial and anticancer potential. The study highlights endophytic fungi as sustainable reservoirs for novel drug candidates and supports the integration of in silico and in vitro approaches in natural product-based drug discovery.