Paraphaeosphaeride D and berkleasmin F, new circumventors of arbekacin resistance in MRSA, produced by Paraphaeosphaeria sp. TR-022

Two new compounds, designated paraphaeosphaeride D ( 1 ) and berkleasmin F ( 2 ) together with a previously known compound, berkleasmin A ( 3 ), isolated from a culture broth of the fungus Paraphaeosphaeria sp. TR-022, proved to be new circumventors of arbekacin (ABK) resistance in methicillin-resistant Staphylococcus aureus (MRSA). The structures of 1 and 2 were elucidated by spectroscopic analyses, including various NMR experiments. All compounds showed 10–100 times ABK circumvention activities using the paper disc method and reduced the MIC values of ABK against MRSA from 16 μg ml −1 to 4 μg ml −1 (fourfold) using the agar dilution method. These new compounds might be promising lead compounds for developing circumventors of ABK resistance in MRSA.