The first low microM SecA inhibitors.
SecA ATPase is a critical member of the Sec family, which is important in the translocation of membrane and secreted polypeptides/proteins in bacteria. Small molecule inhibitors can be very useful research tools as well as leads for future antimicrobial agent development. Based on previous virtual screening work, we optimized the structures of two hit compounds and obtained SecA ATPase inhibitors with IC(50) in the single digit micromolar range. These represent the first low micromolar synthetic inhibitors of bacterial SecA and will be very useful for mechanistic studies.
Chen
Weixuan
W
Department of Chemistry, Georgia State University, Atlanta, GA 30302-4098, USA.
Huang
Ying-ju
YJ
Gundala
Sushma Reddy
SR
Yang
Hsiuchin
H
Li
Minyong
M
Tai
Phang C
PC
Wang
Binghe
B
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D004353:Drug Evaluation, Preclinical; D004926:Escherichia coli / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D026901:Membrane Transport Proteins; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008962:Models, Theoretical; D000069816:SEC Translocation Channels; D000081416:SecA Proteins; D021241:Spectrometry, Mass, Electrospray Ionization
D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D000069816:SEC Translocation Channels; D000251:Adenosine Triphosphatases; D000081416:SecA Proteins