Discovery of antimicrobial citrinin dimers from the mangrove-derived fungus Penicillium citrinum.

Three previously undescribed citrinin dimers, penicitrones A-C (1-3), and one previously unreported tetramic acid derivative, penipyrrone A (4), along with fourteen previously known compounds (5-18) were isolated from the crude extract of the mangrove-derived fungus Penicillium citrinum WHUF05149. The structures of compounds 1-4 were elucidated through comprehensive spectroscopic analyses and their absolute configurations were determined by the modified Snatzke's method and ECD calculations. Compound 3 demonstrated moderate antifungal activities against three strains of Cryptococcus gattii (3284G14, R265 and 3271G1). Compound 15 displayed antibacterial effects against Bacillus subtilis, Bacillus paranthracis and methicillin-resistant Staphylococcus aureus (MRSA) along with anti-biofilm effects against these pathogens. In addition, compound 15 exhibits anti-MRSA activity by disrupting cell membrane integrity, inducing the leakage of intracellular constituents and reducing intracellular ATP levels.