Aaptamines as sortase A inhibitors from the tropical sponge Aaptos aaptos

Four aaptamines (1–4), 1H-benzo[de][1,6]-naphthyridine alkaloids, were isolated from the marine sponge Aaptos aaptos and their inhibitory activities against sortase A (SrtA), an enzyme that plays a key role in cell wall protein anchoring and virulence in Staphylococcus aureus, were evaluated. Isoaaptamine (2) was a potent inhibitor of SrtA, with an IC50 value of 3.7 ± 0.2 μg/mL. The suppression of fibronectin-binding activity by isoaaptamine (2) highlights its potential for the treatment of S. aureus infections via inhibition of SrtA activity. Our studies have identified a series of SrtA inhibitors, providing the basis for further development of potent inhibitors.