Exploration of the structure–activity relationship and druggability of novel oxazolidinone‐based compounds as Gram‐negative antibacterial agents |
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Authors: | Shi Ding Jing‐Chao Ji Ming‐Juan Zhang Yu‐She Yang Rui Wang Xing‐Long Zhu Li‐Hong Wang Yi Zhong Le Gao Man Lu Ju Liu Ye Chen |
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Abstract: | To gain further knowledge of the structure–activity relationship and druggability of novel oxazolidinone‐based UDP‐3‐O‐acyl‐N‐acetylglucosamine deacetylase (LpxC) inhibitors as Gram‐negative antibacterial agents, compounds containing the hydrophobic tails with different lengths and terminal substitutions were synthesized and their antibacterial activities against standard and clinically isolated Gram‐negative strains were evaluated. We summarized their structure–activity relationships and found that oxazolidinone‐based compounds exhibited a narrower antibacterial spectrum compared with threonine‐based compounds. Furthermore, we parallelly compared the metabolic stabilities of the compounds with the classic threonine scaffold and the novel oxazolidinone scaffold in liver microsomes. The results indicated that the druggability of the oxazolidinone scaffold may be inferior to the classic threonine scaffold in the design of LpxC inhibitors. |
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Keywords: | antibacterial activity oxazolidine QSAR |
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