Bacterial Cell Growth Inhibitors Targeting Undecaprenyl Diphosphate Synthase and Undecaprenyl Diphosphate Phosphatase |
| |
| Authors: | Dr Yang Wang Janish Desai Yonghui Zhang Dr Satish R Malwal Christopher J Shin Dr Xinxin Feng Hong Sun Guizhi Liu Prof Rey‐Ting Guo Prof Eric Oldfield |
| |
| Affiliation: | 1. Department of Chemistry, University of Illinois at Urbana–Champaign, Urbana, IL, USA;2. Center for Biophysics and Quantitative Biology, University of Illinois at Urbana–Champaign, Urbana, IL, USA;3. Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China |
| |
| Abstract: | We synthesized a series of benzoic acids and phenylphosphonic acids and investigated their effects on the growth of Staphylococcus aureus and Bacillus subtilis. One of the most active compounds, 5‐fluoro‐2‐(3‐(octyloxy)benzamido)benzoic acid ( 7 , ED50～0.15 μg mL?1) acted synergistically with seven antibiotics known to target bacterial cell‐wall biosynthesis (a fractional inhibitory concentration index (FICI) of ～0.35, on average) but had indifferent effects in combinations with six non‐cell‐wall biosynthesis inhibitors (average FICI～1.45). The most active compounds were found to inhibit two enzymes involved in isoprenoid/bacterial cell‐wall biosynthesis: undecaprenyl diphosphate synthase (UPPS) and undecaprenyl diphosphate phosphatase (UPPP), but not farnesyl diphosphate synthase, and there were good correlations between bacterial cell growth inhibition, UPPS inhibition, and UPPP inhibition. |
| |
| Keywords: | benzoic acids cell-wall biosynthesis drug discovery membrane proteins Staphylococcus aureus |
|
|
