Inhibitors of the aminoglycoside 6¡ä-N-acetyltransferase type Ib [AAC(6¡ä)-Ib] identified by in silico molecular docking
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- 作者：David L. Lin ; Tung Tran ; Christina Adams ; Jamal Y. Alam ; Steven R. Herron ; Marcelo E. Tolmasky
- 关键词：AAC(6&prime ; )-Ib ; aminoglycoside 6&prime ; -N-acetyltransferase type Ib ; acetyl CoA ; acetyl coenzyme A ; DMSO ; dimethyl sulfoxide ; DTNB ; 5 ; 5&prime ; -dithiobis(2-nitrobenzoic acid) ; Vi ; initial velocity
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2013
- 出版时间：15 October, 2013
- 年：2013
- 卷：23
- 期：20
- 页码：5694-5698
- 全文大小：866 K
文摘
AAC(6¡ä)-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¡ä)-Ib and exhibited competitive inhibition against kanamycin A.