Synthesis and antimicrobial activities of oximes derived from O-benzylhydroxylamine as FabH inhibitors.
Forty-three oxime derivatives were synthesized by allowing O-benzylhydroxylamines to react with primary benzaldehydes or salicylaldehydes; these products were gauged as potential inhibitors of β-ketoacyl-(acyl-carrier-protein) synthase III (FabH). Among the 43 compounds, 38 are reported herein for the first time. These compounds were assayed for antimicrobial activities against Escherichia coli, Pseudomonas aeruginosa, Pseudomonas fluorescens, Bacillus subtilis, Staphylococcus aureus, and Enterococcus faecalis. Compounds with prominent antibacterial activities were tested for their E. coli FabH inhibitory activities. 3-((2,4-Dichlorobenzyloxyimino)methyl)benzaldehyde O-2,4-dichlorobenzyl oxime (44) showed the best antibacterial activity, with minimum inhibitory concentrations of 3.13-6.25 μg mL(-1) against the tested bacterial strains, exhibiting the best E. coli FabH inhibitory activity, with an IC(50) value of 1.7 mM. Docking simulations were performed to position compound 44 into the E. coli FabH active site in order to determine the most probable binding conformation.
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
Yin
Y
Luo
Li-Rong
LR
Zhang
Yang
Y
Hu
Shuai
S
Zhang
Jie
J
Fu
Xiao-Ming
XM
Wang
Hai-Liang
HL
Zhu
D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; D000123:Acetyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054889:Fatty Acid Synthase, Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D006898:Hydroxylamines / Q000737:chemistry; D062105:Molecular Docking Simulation; D010091:Oximes / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D006898:Hydroxylamines; D010091:Oximes; C017064:benzyloxyamine; D000123:Acetyltransferases; C557158:fabH protein, E coli; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; D054889:Fatty Acid Synthase, Type II