Cationic Anthraquinone Analogs as Selective Antimicrobials.

Abstract

Development of new antibiotics is always needed in the fight against growing threat from multiple drug–resistant bacteria, such as resistant Gram-negative (G−) Escherichia coli and Klebsiella pneumoniae. While the development of broad-spectrum antibiotics has attracted great attention, careful administration of these antibiotics is important to avoid adverse effects, like Clostridium difficile infection (CDI). The use of broad-spectrum antibiotics, for example, quinolones, can increase the risk of CDI by eradicating the protective bacteria in intestine and encouraging C difficile spore germination. Many common intestine bacteria are G− or anaerobic, including Enterococcus faecalis, Bacteroides fragilis, and E coli. Hence, it may be advantageous in certain therapeutic practices to employ selective antimicrobials. For instance, Gram-positive (G+) methicillin-resistant Staphylococcus aureus (MRSA) that can cause life-threatening sepsis can be controlled with the use of selective antibiotic, vancomycin. Nevertheless, its effectiveness has been limited with the emerging of vancomycin-resistant Staphylococcus aureus (VRSA). A recent report on antimicrobial cationic anthraquinone analogs (CAAs) that show tunable activity and selectivity may provide new hope in the search for selective antimicrobials. In particular, the lead CAA displays prominent activity against MRSA while manifesting low activity against E coli and low cytotoxicity toward normal mammalian cells.