Water Soluble-Nitrogenous Secondary Metabolites From Talaromyces annesophieae MD2 Exhibit Anti-Bacterial, Anti-Cancer, Anti-Oxidant, and Cytoprotective Activities

This study focused on biological activities and chemical characterization of secondary metabolites from the fungus Talaromyces annesophieae MD2 (GenBank: PQ252671). The dichloromethane extract (DCM-E) of its culture supernatant was fractionated using chromatographic techniques. Initially, three main fractions were first prepared from DCM-E. Subsequently, the selected active fraction 2 was subfractionated into six subfractions. The subfraction 3 demonstrated high water solubility and strong antibacterial activity against both gram-positive and gram-negative bacteria (MIC values of 105.41, 82.76, 71.92, and 70.38 µg/mL against B. cereus, S. aureus, E. coli, and K. pneumoniae, respectively). It exhibited selective anticancer activity through regulation of autophagy- and apoptosis-related pathways without affecting healthy cells (IC50 values of 7.65, 3.76, 10.76 µg/mL against HT-29, DU-145 and SH-SY5Y, respectively). Furthermore, it exhibited DPPH and ABTS radical-scavenging activities (48.3% and 44.1% at the concentration of 100 μg/mL, respectively) and protected dermal fibroblasts against H2O2–induced toxicity. Structural analyses elucidated that the subfraction 3 contained four nitrogenous polar compounds. Three compounds (C5H3O4N8, C15H25O4N4, and C23H21N4) were suggested to be alkaloid-like or nitrogen-rich heterocyclic secondary metabolites, while the remaining compound (C9H9O4N) was probably an aminobenzoic acid-type or heteroaromatic carboxylic acid derivative. This is the first report on bioactive metabolites of T. annesophieae. Due to multifunctional biological activities, its metabolites can find application in dermocosmetics and pharmacology. © 2026 The Author(s). MicrobiologyOpen published by John Wiley & Sons Ltd.