Work

Bio-guided discovery of antibacterial metabolites from Penicillium chrysogenum

Year: 2025

Type: article

Abstract: Bio-guided isolation from the Red Sea-derived Penicillium chrysogenum yielded two new metabolites, 15-deoxy-15-amino-citreohybridonol (6) and chrysogenotoxin (7), alongside five known compounds: emodin (1), chrysophanol (2), bis(2-ethylhexyl) phthalate (3), haenamindole (4), and citreorosein (5). Compound 6 exhibited broad-spectrum antibacterial activity against both Gram-positive (MIC: 0.31–0.62 μM; MBC: 0.31–0.62 μM) and Gram-negative bacteria (MIC: 0.15–1.25 μM; MBC: 0.62–2.5 μM). Compound 7 showed potent bactericidal activity against Gram-negative bacteria (MIC: 0.07–0.31 μM; MBC: 0.15–0.62 μM) with MBC/MIC ≤ 4, while compound 4 selectively inhibited S. pneumoniae (MIC: 0.31 μM; MBC: 0.62 μM). Compounds 4, 6, and 7 exhibited low cytotoxicity towards human intestinal epithelial cells (HIEC-6). Molecular docking studies targeting the NDM-1 β-lactamase identified compounds 4, 6, and 7 as potential inhibitors of New Delhi metallo-β-lactamase-1 (NDM-1). Molecular dynamics simulations confirmed the structural stability of 7 within the NDM-1 active site. Chrysogenotoxin (7) was suggested as a promising antibacterial candidate against antibiotic-resistant pathogens.

Source: Journal of Enzyme Inhibition and Medicinal Chemistry

DOI: 10.1080/14756366.2025.2547258