Bis(indole) alkaloids as sortase A inhibitors from the sponge Spongosorites sp.

A new bis(indole) alkaloid (9) of the hamacanthin class along with the previously reported compounds of the related structural classes, topsentin class (1–4) and hamacanthin class (5–8), was isolated from the marine sponge Spongosorites sp. and their inhibitory activities toward sortase A (SrtA) that play key roles in cell-wall protein anchoring and virulence in Staphylococcus aureus were evaluated. Our studies have identified a series of SrtA inhibitors, providing the basis for further development of potent inhibitors. The preliminary structure–activity relationship, to elucidate the essential structural requirements, has been described. The fibronectin-binding activity data highlight the potential of these compounds for the treatment of S. aureus infections via inhibition of SrtA activity.