| Literature DB >> 24011645 |
David L Lin1, Tung Tran, Christina Adams, Jamal Y Alam, Steven R Herron, Marcelo E Tolmasky.
Abstract
AAC(6')-Ib is an important aminoglycoside resistance enzyme to target with enzymatic inhibitors. An in silico screening approach was used to identify potential inhibitors from the ChemBridge library. Several compounds were identified, of which two of them, 4-[(2-{[1-(3-methylphenyl)-4,6-dioxo-2-thioxotetrahydro-5(2H)-pyrimidinylidene]methyl}phenoxy)methyl]benzoic acid and 2-{5-[(4,6-dioxo-1,3-diphenyl-2-thioxotetrahydro-5(2H)-pyrimidinylidene)methyl]-2-furyl}benzoic acid, showed micromolar activity in inhibiting acetylation of kanamycin A. These compounds are predicted to bind the aminoglycoside binding site of AAC(6')-Ib and exhibited competitive inhibition against kanamycin A.Entities:
Keywords: 5,5′-dithiobis(2-nitrobenzoic acid); AAC(6′)-Ib; Acetyltransferase; Aminoglycoside modifying enzymes; Aminoglycoside resistance; DMSO; DTNB; Enterobacteria; Inhibitor; Klebsiella; V(i); acetyl CoA; acetyl coenzyme A; aminoglycoside 6′-N-acetyltransferase type Ib; dimethyl sulfoxide; initial velocity
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Year: 2013 PMID： 24011645 PMCID： PMC3821527 DOI： 10.1016/j.bmcl.2013.08.016
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823