Premium
Exploration of the structure–activity relationship and druggability of novel oxazolidinone‐based compounds as Gram‐negative antibacterial agents
Author(s) -
Ding Shi,
Ji JingChao,
Zhang MingJuan,
Yang YuShe,
Wang Rui,
Zhu XingLong,
Wang LiHong,
Zhong Yi,
Gao Le,
Lu Man,
Liu Ju,
Chen Ye
Publication year - 2019
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201900129
Subject(s) - druggability , gram , antibacterial activity , chemistry , structure–activity relationship , gram negative bacteria , stereochemistry , gram positive bacteria , n gram , combinatorial chemistry , computational biology , bacteria , biochemistry , biology , in vitro , antibiotics , escherichia coli , computer science , genetics , artificial intelligence , gene , language model
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.