Exploration of the structure–activity relationship and druggability of novel oxazolidinone‐based compounds as Gram‐negative antibacterial agents. Issue 11 (3rd September 2019)

• Record Type: Journal Article
• Authors: Ding, Shi; Ji, Jing‐Chao; Zhang, Ming‐Juan; Yang, Yu‐She; Wang, Rui; Zhu, Xing‐Long; Wang, Li‐Hong; Zhong, Yi; Gao, Le; Lu, Man; Liu, Ju; Chen, Ye
• Is Part Of: Archiv der Pharmazie. Volume 352:Issue 11(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-09-03
• Subjects: antibacterial activity -- oxazolidine -- QSAR; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201900129
• Languages: English
• ISSNs: 0365-6233

Abstract

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. Abstract : The structure–activity relationship and druggability of novel oxazolidinone‐based compounds were synthesized and evaluated for their activity against Gram‐negative bacteria. The compounds containing the novel oxazolidinone scaffold exhibit a narrower antibacterial spectrum and worse biological metabolism stability in liver microsomes compared to compounds containing the classic threonine scaffold, indicating that the oxazolidinone scaffold may be inferior to the threonine scaffold in the design of UDP‐3‐ O ‐acyl‐ N ‐acetylglucosamine deacetylase inhibitors.