Abstract：
:Drug-resistant bacterial infections and lack of available antibacterial agents in clinical practice are becoming serious risks to public health. We synthesized a new class of haloemodins by modifying a traditional Chinese medicine component, emodin. The novel haloemodin exerts strong inhibitory activity on bacterial topoisomerase I and DNA gyrase, and not on the topoisomerases of human origin. In principle, it shows remarkable antibacterial activities against laboratory and clinically isolated Gram-positive bacteria, including vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus. We further expanded its antibacterial spectrum into against Gram-negative bacteria with the assistance of polymyxin B nonapeptide, which helps haloemodin to penetrate through the bacterial outer membrane. Finally, the therapeutic effect of haloemodin in vivo was confirmed in curing S. aureus-induced keratitis on rabbit model. With distinctive structural difference from the antibiotics we used, the haloemodins are of value as promising antibacterial pharmacophore, especially for combat the infections caused by drug-resistant pathogens.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Duan F,Li X,Cai S,Xin G,Wang Y,Du D,He S,Huang B,Guo X,Zhao H,Zhang R,Ma L,Liu Y,Du Q,Wei Z,Xing Z,Liang Y,Wu X,Fan C,Ji C,Zeng D,Chen Q,He Y,Liu X,Huang Wdoi
10.1021/jm401685fsubject
Has Abstractpub_date
2014-05-08 00:00:00pages
3707-14issue
9eissn
0022-2623issn
1520-4804journal_volume
57pub_type
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