Aaptamines as sortase A inhibitors from the tropical sponge Aaptos aaptos

Sortase A: An ideal target for anti-virulence drug development

“…and evaluated for their inhibitory activity against S. aureus SrtA [60]. Among 9 isolated [1,6]-naphthyridine alkaloids that were isolated from the Aaptos aaptos marine sponge [61]. Increased antiSrtA activity was observed for isoaaptamin (IC 50 ¼ 3.7 ± 0.2 mg/ml) and the importance of the methyl group at the N-1 position was demonstrated for SrtA inhibitory activity by this class of natural compounds.…”

New Thiazole Nortopsentin Analogues Inhibit Bacterial Biofilm Formation

“…The 2-aminoimidazole oroidin, a marine alkaloid, isolated from the marine sponge Agelas conifer , and its analogues are studied for antibiofilm activity [11]. Sortase A (SrtA), a transpeptidase involved in the anchoring of surface proteins to the Gram-positive bacterial cell wall, plays a key role in bacterial adhesion, immune evasion and biofilm formation [12,13]. 1 H -Benzo[de][1,6]-naphthyridine alkaloid isoaaptamine, isolated from the marine sponge Aaptos aaptos [14], was reported to be a potent inhibitor of SrtA (IC 50 value of 3.7 µM).…”

Probing of the cis-5-phenyl proline scaffold as a platform for the synthesis of mechanism-based inhibitors of the Staphylococcus aureus sortase SrtA isoform

“…The same effect has been demonstrated for wild gram-positive organisms treated with sortase inhibitors, implicating sortase enzymes as important targets for the treatment of staphylococcal disease 2. Different types of sortase inhibitors have been recently reviewed,3 and the most active and promising small-molecule inhibitors4-12 are presented in Figure 1. Three types of small molecules, aryl (β-amino)ethyl ketones,7 trans -3-(furan-2-yl) acrylic acid amides8 and aaptamines,12 have been reported since the publication of the review.…”

“…Different types of sortase inhibitors have been recently reviewed,3 and the most active and promising small-molecule inhibitors4-12 are presented in Figure 1. Three types of small molecules, aryl (β-amino)ethyl ketones,7 trans -3-(furan-2-yl) acrylic acid amides8 and aaptamines,12 have been reported since the publication of the review. This work describes our studies towards the design and synthesis of novel types of S. aureus SrtA inhibitors, and an understanding of their mechanisms of action.…”