Two new thiodiketopiperazines (TDKPs), designated graphiumins I (1) and J (2), were isolated from the culture broth of the marine-derived fungus Graphium sp. OPMF00224 by solvent extraction, silica gel column chromatography, and HPLC. Their absolute structures were elucidated by spectroscopic analyses (1D and 2D NMR data, ROESY correlations, and CD data) and chemical methods. They were found to be structurally rare TDKPs with a phenylalanine-derived indolin substructure. Compounds 1 and 2 inhibited yellow pigment production by methicillin-resistant Staphylococcus aureus (MRSA) with IC50 values of 63.5 and 76.5 microg/ml, respectively, without inhibiting its growth, even at 250 microg/ml.
Chromatography ; Chromatography, High Pressure Liquid ; Fungi* ; Inhibitory Concentration 50 ; Methicillin-Resistant Staphylococcus aureus ; Silica Gel

In an analytical study of microbial broths, the actinomycete strain Kitasatospora sp. P07101 was found to produce three new congeners, which were designated hazimycins B (1), C (2), and D (3), together with the previously reported hazimycin (renamed hazimycin A (4)). The structures of these hazimycins were examined using various spectroscopic methods including nuclear magnetic resonance (NMR), and the results revealed that 1-3 were analogues of hazimycin with the replacement of one of the two isonitrile groups in 4 by an NH-formyl group in 1, the two isonitrile groups and an amide group by two NH-formyl groups and a nitrile group in 2, and the two isonitrile groups and two amide groups by two NH-formyl groups and two nitrile groups in 3. Only hazimycin A exhibited moderate antimicrobial activities against Gram-positive bacteria and Candida albicans. These results indicated that the presence of two isonitrile groups in the hazimycin structure is essential for antimicrobial activity.

2-Hydroxytyrosol (2-HT), originally reported as a synthetic compound, was isolated for the first time as a fungal metabolite. 2-HT was found to inhibit mushroom tyrosinase with an IC50 value of 13.0 µmol/L. Furthermore, 2-HT dose-dependently inhibited tyrosinase activity (IC50, 32.5 µmol/L) in the cell-free extract of B16 melanoma cells and α-melanocyte stimulating hormone (α-MSH)-stimulated melanin formation in intact B16 melanoma cells.