title: Design, synthesis, and evaluation of efflux substrate-metal chelator conjugates as potential antimicrobial agents.
abstract: Maintaining a proper balance of metal concentrations is critical to the survival of bacteria. We have designed and synthesized a series of conjugates of metal chelators and efflux transporter substrates aimed at disrupting bacterial metal homeostasis to achieve bacterial killing. Biological studies showed that two of the compounds had very significant antimicrobial effect with an MIC value of 7.8 microg/mL against Gram-positive Bacillus subtilis.
authors.affiliation: Department of Chemistry, Center for Biotechnology and Drug Design, Georgia State University, Atlanta, GA 30302-4098, USA.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Eric Ballard
authors.forename: Shi-Long
authors.initials: SL
authors.lastname: Zheng
authors.forename: Xingming
authors.initials: X
authors.lastname: Gao
authors.forename: Ko-Chun
authors.initials: KC
authors.lastname: Ko
authors.forename: Hsiuchin
authors.initials: H
authors.lastname: Yang
authors.forename: Gary
authors.initials: G
authors.lastname: Brandt
authors.forename: Xinhui
authors.initials: X
authors.lastname: Lou
authors.forename: Phang C
authors.initials: PC
authors.lastname: Tai
authors.forename: Chung-Dar
authors.initials: CD
authors.lastname: Lu
authors.forename: Binghe
authors.initials: B
authors.lastname: Wang
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D024901:Drug Resistance, Multiple, Bacterial; D004926:Escherichia coli / Q000187:drug effects; D007202:Indicators and Reagents; D008670:Metals / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D002614:Chelating Agents; D007202:Indicators and Reagents; D008670:Metals