Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/19994
Title: Structure-based design, synthesis, and biological evaluation of Isatin derivatives as potential glycosyltransferase inhibitors
Authors: Wang, Y
Chan, FY
Sun, N
Lui, HK
So, PK
Yan, SC
Chan, KF 
Chiou, J
Chen, S
Abagyan, R
Leung, YC 
Wong, KY 
Keywords: Antibacterial activity
Glycosyltransferase
Isatin derivatives
STD-NMR
Virtual screening
Issue Date: 2014
Source: Chemical biology and drug design, 2014 How to cite?
Journal: Chemical Biology and Drug Design 
Abstract: Peptidoglycan glycosyltransferase (PGT) has been shown to be an important pharmacological target for the inhibition of bacterial cell wall biosynthesis. Structure-based virtual screening of about 3 000 000 commercially available compounds against the crystal structure of the glycosyltransferase (GT) domain of the Staphylococcus aureus penicillin-binding protein 2 (S. aureus PBP2) resulted in identification of an isatin derivative, 2-(3-(2-carbamimidoylhydrazono)-2-oxoindolin-1-yl)-N-(m-tolyl)acetamide (4) as a novel potential GT inhibitor. A series of 4 derivatives were synthesized. Several compounds showed more active antimicrobial activity than the initial hit compound 4, in particular 2-(3-(2-carbamimidoylhydrazono)-2-oxoindolin-1-yl)-N-(3-nitrophenyl)acetamide (4l), against Gram-positive Bacillus subtilis and S. aureus with MIC values of 24 and 48 £gg/mL, respectively. Saturation transfer difference (STD) NMR study revealed that there is a binding contact between 4l and the GT domain of S. aureus PBP2. Competitive STD-NMR further proved that 4l and moenomycin A bind to GT domain in a competitive manner. Molecular docking study suggests a potential bi
URI: http://hdl.handle.net/10397/19994
ISSN: 1747-0277
DOI: 10.1111/cbdd.12361
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