title: Bis(indole) alkaloids as sortase A inhibitors from the sponge Spongosorites sp.
abstract: 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.
authors.affiliation: School of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Korea.
authors.forename: Ki-Bong
authors.initials: KB
authors.lastname: Oh
authors.forename: Woongchon
authors.initials: W
authors.lastname: Mar
authors.forename: Sanghee
authors.initials: S
authors.lastname: Kim
authors.forename: Ji-Yun
authors.initials: JY
authors.lastname: Kim
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Oh
authors.forename: Jae-Gyu
authors.initials: JG
authors.lastname: Kim
authors.forename: Daehyun
authors.initials: D
authors.lastname: Shin
authors.forename: Chung J
authors.initials: CJ
authors.lastname: Sim
authors.forename: Jongheon
authors.initials: J
authors.lastname: Shin
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D019881:Aminoacyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003546:Cysteine Endopeptidases; D005353:Fibronectins / Q000378:metabolism; D007211:Indoles / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry*; D011485:Protein Binding; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology
chemical_list: D000470:Alkaloids; D001426:Bacterial Proteins; D005353:Fibronectins; D007211:Indoles; C030374:indole; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases