title: Haloemodin as novel antibacterial agent inhibiting DNA gyrase and bacterial topoisomerase I.
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.
authors.affiliation: Laboratory of Ethnopharmacology, Institute for Nanobiomedical Technology and Membrane Biology, Regenerative Medicine Research Center, West China Hospital, West China Medical School, Sichuan University Keyuan 4 Road No. 1, Gaopeng Avenue, Gaoxinqu, Chengdu, Sichuan 610041 China.
authors.forename: Feixia
authors.initials: F
authors.lastname: Duan
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.forename: Suping
authors.initials: S
authors.lastname: Cai
authors.forename: Guang
authors.initials: G
authors.lastname: Xin
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Du
authors.forename: Shiliang
authors.initials: S
authors.lastname: He
authors.forename: Baozhan
authors.initials: B
authors.lastname: Huang
authors.forename: Xiurong
authors.initials: X
authors.lastname: Guo
authors.forename: Hang
authors.initials: H
authors.lastname: Zhao
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Limei
authors.initials: L
authors.lastname: Ma
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Qigen
authors.initials: Q
authors.lastname: Du
authors.forename: Zeliang
authors.initials: Z
authors.lastname: Wei
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Xing
authors.forename: Yong
authors.initials: Y
authors.lastname: Liang
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Wu
authors.forename: Chengzhong
authors.initials: C
authors.lastname: Fan
authors.forename: Chengjie
authors.initials: C
authors.lastname: Ji
authors.forename: Dequan
authors.initials: D
authors.lastname: Zeng
authors.forename: Qianming
authors.initials: Q
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: He
authors.forename: Xuyang
authors.initials: X
authors.lastname: Liu
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004642:Emodin / Q000031:analogs & derivatives* / Q000494:pharmacology; D016984:Enterococcus faecium / Q000187:drug effects* / Q000201:enzymology; D007634:Keratitis / Q000188:drug therapy / Q000382:microbiology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D059004:Topoisomerase I Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D004642:Emodin