Discovery of quinoline small molecules with potent dispersal activity against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis biofilms using a scaffold hopping strategy

作者：Abouelhassan Yasmeen; Garrison Aaron T; Burch Gena M; Wong Wilson; Norwood Verrill M; Huigens Robert W III^*

来源：Bioorganic & Medicinal Chemistry Letters, 2014, 24(21): 5076-5080.

DOI：10.1016/j.bmcl.2014.09.009

• Drug discovery
• Biofilm dispersal agent
• Biofilm inhibitor
• Antibacterial agent
• Quinoline

Staphylococcus aureus and Staphylococcus epidermidis are recognized as the most frequent cause of biofilm-associated nosocomial and indwelling medical device infections. Biofilm-associated infections are known to be highly resistant to our current arsenal of clinically used antibiotics and antibacterial agents. To exacerbate this problem, no therapeutic option exists that targets biofilm-dependent machinery critical to Staphylococcal biofilm formation and maintenance. Here, we describe the discovery of a series of quinoline small molecules that demonstrate potent biofilm dispersal activity against methicillin-resistant S. aureus and S. epidermidis using a scaffold hopping strategy. This interesting class of quinolines also has select synthetic analogues that demonstrate potent antibacterial activity and biofilm inhibition against S. aureus and S. epidermidis.

• 出版日期2014-11-1