Potent antibacterial and cytotoxic bioactive compounds from endophytic fungi Diaporthe sp. associated with Salacia intermedia

Antibacterial screening of endophytic fungi from Salacia intermedia identified Diaporthe longicolla as a potent strain exhibiting good activity against multidrug-resistant Staphylococcus aureus and Pseudomonas aeruginosa, with an MIC of 39.1 µg/mL. Scale-up fermentation and chromatographic purification of this strain yielded three known compounds, which were cytochalasin J (1), cytochalasin H (2), and dicerandrol C (3), as identified by liquid chromatography – high mass resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR) spectroscopy. Among those compounds, dicerandrol C exhibited broad-spectrum antibacterial activity against ATCC and multidrug-resistant strains of Bacillus subtilis, S. aureus, and P. aeruginosa, and multidrug-resistant strains of Klebsiella pneumoniae and Escherichia coli, with MIC values ranging from 1.04 to 33.30 µM. Furthermore, dicerandrol C outperformed tetracycline in antibacterial efficacy against S. aureus ATCC 6538 and methicillin-resistant S. aureus (MRSA) strains (MIC of 1.04 µM). Further antibacterial evaluation showed that cytochalasin J (221.43 µM), cytochalasin H (202.59 µM), and dicerandrol C (tested at its MIC values of 1.04 µM for S. aureus ATCC 6538 and 16.65 µM for P. aeruginosa ATCC 15442) significantly inhibited bacterial biofilm formation. The biofilm inhibition percentages ranged from 61.09 to 78.17% for S. aureus and 41.22–56.83% for P. aeruginosa. In cytotoxicity assays against MCF-7 cells, all three compounds reduced cell viability (48.68–74.50%), with dicerandrol C demonstrating the highest potency. These findings highlight the potential of dicerandrol C as a powerful antibacterial and cytotoxic agent, facilitating further investigations into its therapeutic applications.