Discovery of (phenylureido)piperidinyl benzamides as prospective inhibitors of bacterial autolysin E from Staphylococcus aureus

Journal of Enzyme Inhibition and Medicinal Chemistry
Jure BorišekMarjana Novič

Abstract

Autolysin E (AtlE) is a cell wall degrading enzyme that catalyzes the hydrolysis of the β-1,4-glycosidic bond between the N-acetylglucosamine and N-acetylmuramic acid units of the bacterial peptidoglycan. Using our recently determined crystal structure of AtlE from Staphylococcus aureus and a combination of pharmacophore modeling, similarity search, and molecular docking, a series of (Phenylureido)piperidinyl benzamides were identified as potential binders and surface plasmon resonance (SPR) and saturation-transfer difference (STD) NMR experiments revealed that discovered compounds bind to AtlE in a lower micromolar range. (phenylureido)piperidinyl benzamides are the first reported non-substrate-like compounds that interact with this enzyme and enable further study of the interaction of small molecules with bacterial AtlE as potential inhibitors of this target.

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Citations

Nov 30, 2018·Medical Microbiology and Immunology·Vigyasa Singh, Ujjal Jyoti Phukan
Jul 1, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Thaís da Silva MoraesCarlos Henrique Gomes Martins

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Methods Mentioned

BETA
surface
NMR
chip
in silico techniques
irradiate

Software Mentioned

CHEMPLP
SPR
Varian
GOLD Suite
GOLD
eMolecules
Ligandscout
AtlE
OMEGA

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