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ID: ALA1139657

Journal: Bioorg Med Chem Lett

Title: Isothiazoloquinolones containing functionalized aromatic hydrocarbons at the 7-position: synthesis and in vitro activity of a series of potent antibacterial agents with diminished cytotoxicity in human cells.

Authors: Wiles JA, Wang Q, Lucien E, Hashimoto A, Song Y, Cheng J, Marlor CW, Ou Y, Podos SD, Thanassi JA, Thoma CL, Deshpande M, Pucci MJ, Bradbury BJ.

Abstract: This report describes 9H-isothiazolo[5,4-b]quinoline-3,4-diones (ITQs) containing aromatic groups at the 7-position that were prepared using palladium-catalyzed cross-coupling and tested against a panel of susceptible and resistant bacteria. In general, these compounds were more effective against Gram-positive than Gram-negative organisms. Many of the ITQs were more potent than contemporary quinolones and displayed a particularly strong antistaphylococcal activity against a clinically important, multi-drug-resistant strain. In contrast with ITQs reported previously, several of the analogues described in this Letter demonstrated low cytotoxic activity against a human cell line.

CiteXplore: 16337791

DOI: 10.1016/j.bmcl.2005.11.065