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.