Bacterial Cell Growth Inhibitors Targeting Undecaprenyl Diphosphate Synthase and Undecaprenyl Diphosphate Phosphatase

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• 作者：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 and Prof. Eric Oldfield
• 刊名：ChemMedChem
• 出版年：2016
• 出版时间：October 19, 2016
• 年：2016
• 卷：11
• 期：20
• 页码：2311-2319
• 全文大小：1232K
• ISSN：1860-7187

文摘

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.