Antimicrobial alkaloids produced by the mangrove endophyte Penicillium brocae MA-231 using the OSMAC approach

The OSMAC (one strain-many compounds) protocol was used in this study to obtain various metabolites from the mangrove-derived endophytic fungus Penicillium brocae MA-231. As a result, four new thiodiketopiperazine alkaloids, penicibrocazines F-I (1-4), together with two new N-containing p-hydroxyphenopyrrozin derivatives brocapyrrozins A and B (7 and 8) as well as six known alkaloids (5, 6, and 9-12), were identified from the extract of the Czapek culture medium of the fungus. Their structures and absolute configurations were determined through interpretation of their spectroscopic data and by X-ray crystallographic analysis. Compounds 7 and 9 exhibited potent activity against human pathogenic bacterium Staphylococcus aureus with MIC values of 0.125 and 0.5 mg mL(-1), respectively.