title: Aaptamines as sortase A inhibitors from the tropical sponge Aaptos aaptos.
abstract: 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 IC(50) value of 3.7+/-0.2 microg/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.
authors: Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 110-460, Republic of Korea.
authors: Kyoung Hwa
authors: KH
authors: Jang
authors: Soon-Chun
authors: SC
authors: Chung
authors: Jongheon
authors: J
authors: Shin
authors: So-Hyoung
authors: SH
authors: Lee
authors: Tae-Im
authors: TI
authors: Kim
authors: Hyi-Seung
authors: HS
authors: Lee
authors: Ki-Bong
authors: KB
authors: Oh
mesh_terms: D019881:Aminoacyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003546:Cysteine Endopeptidases; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D005353:Fibronectins / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000302:isolation & purification / Q000494:pharmacology*; D011161:Porifera / Q000737:chemistry*; D011485:Protein Binding; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D005353:Fibronectins; D009287:Naphthyridines; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases; C043986:aaptamine