Identification of multi-target lead compounds from iron-stressed Aspergillus species using LC-MS, in silico analysis, and pharmacokinetics profiling.

Natural products from soil-derived fungi represent an important source of bioactive compounds with therapeutic potential. In this study, Aspergillus spp. isolated from soil samples were cultured under iron-limited conditions to stimulate siderophore-associated secondary metabolism. Three lead metabolites, Unguisin E, Austalide Q, and Notoamide J, were characterised using LC-MS analysis. Their therapeutic relevance was evaluated through molecular docking against EGFR tyrosine kinase (1M17), PPAR-γ (PDB IDs: 2PRG and 2HNP), and DNA gyrase (1KZN) representing anticancer, antidiabetic and antimicrobial targets. The metabolites exhibited notable binding affinities comparable to standard drugs, including Erlotinib and Rosiglitazone. Austalide Q and Notoamide J showed stable interactions within the active sites of both proteins. Pharmacokinetic and toxicity predictions using SwissADME, pkCSM, and ProTox-3.0 indicated favourable drug-likeness, high intestinal absorption, and no predicted hepatotoxicity or immunotoxicity. Overall, these findings suggest that Aspergillus-derived metabolites may serve as promising candidates for future antimicrobial and therapeutic drug discovery studies.