Synthesis, SAR and molecular docking study of novel non-β-lactam inhibitors of TEM type β-lactamase

Roman L Antipin; Daria A Beshnova; Rostislav A Petrov; Anna S Shiryaeva; Irina P Andreeva; Vitaly G Grigorenko; Maya Yu Rubtsova; Alexander G Majouga; Victor S Lamzin; Alexey M Egorov

doi:10.1016/j.bmcl.2017.02.025

Synthesis, SAR and molecular docking study of novel non-β-lactam inhibitors of TEM type β-lactamase

Bioorg Med Chem Lett. 2017 Apr 1;27(7):1588-1592. doi: 10.1016/j.bmcl.2017.02.025. Epub 2017 Feb 16.

Affiliations

¹ Chemistry Department, M.V. Lomonosov Moscow State University, Lenin Hills, 1, bld. 3, Moscow 119991, Russia. Electronic address: [email protected].
² European Molecular Biology Laboratory (EMBL), c/o DESY, Notkestrasse 85, Hamburg 22607, Germany.
³ Chemistry Department, M.V. Lomonosov Moscow State University, Lenin Hills, 1, bld. 3, Moscow 119991, Russia.
⁴ Chemistry Department, M.V. Lomonosov Moscow State University, Lenin Hills, 1, bld. 3, Moscow 119991, Russia; National University of Science and Technology MISiS, Leninsky ave. 4, Moscow 119049, Russia.

PMID: 28237762
DOI: 10.1016/j.bmcl.2017.02.025

Abstract

The novel classes of acylated phenoxyanilide and thiourea compounds were investigated for their ability to inhibit TEM type β-lactamase enzyme. Two compounds 4g and 5c reveal the inhibition potency in micromolar range and show their action by non-covalent binding in the vicinity of the TEM-171 active site. The structure activity relationship around carbon chain length and different substituents in ortho- and para-positions of acylated phenoxyanilide as well as molecular modelling study has been performed.

Keywords: Acylated phenoxyaniline; Molecular docking; TEM type β-lactamase; Thiourea; β-Lactamase inhibitors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anilides / chemistry
Catalytic Domain
Escherichia coli Proteins / antagonists & inhibitors*
Escherichia coli Proteins / chemistry
Hydrogen Bonding
Kinetics
Molecular Docking Simulation
Phenyl Ethers / chemistry
Structure-Activity Relationship
Thiourea / analogs & derivatives*
Thiourea / chemistry
beta-Lactamase Inhibitors / chemistry*
beta-Lactamases / chemistry*

Substances

4-((4-(2,4-dichloro)phenoxyphenyl)-4-carboxyphenyl)thiourea
Anilides
Escherichia coli Proteins
Phenyl Ethers
beta-Lactamase Inhibitors
beta-Lactamases
beta-lactamase TEM-171, E coli
Thiourea