Jump to main content
Jump to site search
Access to RSC content Close the message box

Continue to access RSC content when you are not at your institution. Follow our step-by-step guide.


Issue 1, 2016
Previous Article Next Article

Identification of an inhibitor of the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib] by glide molecular docking

Author affiliations

Abstract

The aminoglycoside 6′-N-acetyltransferase type Ib, AAC(6′)-Ib, confers resistance to clinically relevant aminoglycosides and is the most widely distributed enzyme among AAC(6′)-I-producing Gram-negative pathogens. An alternative to counter the action of this enzyme is the development of inhibitors. Glide is a computational strategy for rapidly docking ligands to protein sites and estimating their binding affinities. We docked a collection of 280 000 compounds from 7 sub-libraries of the Chembridge library as ligands to the aminoglycoside binding site of AAC(6′)-Ib. We identified a compound, 1-[3-(2-aminoethyl)benzyl]-3-(piperidin-1-ylmethyl)pyrrolidin-3-ol (compound 1), that inhibited the acetylation of aminoglycosides in vitro with IC50 values of 39.7 and 34.9 μM when the aminoglycoside substrates assayed were kanamycin A or amikacin, respectively. The growth of an amikacin-resistant Acinetobacter baumannii clinical strain was inhibited in the presence of a combination of amikacin and compound 1.

Graphical abstract: Identification of an inhibitor of the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib] by glide molecular docking

Back to tab navigation

Supplementary files

Article information


Submitted
30 Jul 2015
Accepted
03 Nov 2015
First published
16 Nov 2015

Med. Chem. Commun., 2016,7, 184-189
Article type
Concise Article

Identification of an inhibitor of the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib] by glide molecular docking

K. Chiem, S. Jani, B. Fuentes, D. L. Lin, M. E. Rasche and M. E. Tolmasky, Med. Chem. Commun., 2016, 7, 184
DOI: 10.1039/C5MD00316D

Search articles by author

Spotlight

Advertisements