Design, synthesis, and evaluation of efflux substrate-metal chelator conjugates as potential antimicrobial agents.
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.
Zhang
Yanling
Y
Department of Chemistry, Center for Biotechnology and Drug Design, Georgia State University, Atlanta, GA 30302-4098, USA.
Eric Ballard
C
C
Zheng
Shi-Long
SL
Gao
Xingming
X
Ko
Ko-Chun
KC
Yang
Hsiuchin
H
Brandt
Gary
G
Lou
Xinhui
X
Tai
Phang C
PC
Lu
Chung-Dar
CD
Wang
Binghe
B
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
D000900:Anti-Bacterial Agents; D002614:Chelating Agents; D007202:Indicators and Reagents; D008670:Metals