title: Synthesis, SAR and molecular docking study of novel non-β-lactam inhibitors of TEM type β-lactamase.
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.
authors.affiliation: Chemistry Department, M.V. Lomonosov Moscow State University, Lenin Hills, 1, bld. 3, Moscow 119991, Russia. Electronic address: antipin@org.chem.msu.ru.
authors.forename: Roman L
authors.initials: RL
authors.lastname: Antipin
authors.affiliation: European Molecular Biology Laboratory (EMBL), c/o DESY, Notkestrasse 85, Hamburg 22607, Germany.
authors.forename: Daria A
authors.initials: DA
authors.lastname: Beshnova
authors.affiliation: Chemistry Department, M.V. Lomonosov Moscow State University, Lenin Hills, 1, bld. 3, Moscow 119991, Russia.
authors.forename: Rostislav A
authors.initials: RA
authors.lastname: Petrov
authors.affiliation: Chemistry Department, M.V. Lomonosov Moscow State University, Lenin Hills, 1, bld. 3, Moscow 119991, Russia.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Shiryaeva
authors.affiliation: Chemistry Department, M.V. Lomonosov Moscow State University, Lenin Hills, 1, bld. 3, Moscow 119991, Russia.
authors.forename: Irina P
authors.initials: IP
authors.lastname: Andreeva
authors.affiliation: Chemistry Department, M.V. Lomonosov Moscow State University, Lenin Hills, 1, bld. 3, Moscow 119991, Russia.
authors.forename: Vitaly G
authors.initials: VG
authors.lastname: Grigorenko
authors.affiliation: Chemistry Department, M.V. Lomonosov Moscow State University, Lenin Hills, 1, bld. 3, Moscow 119991, Russia.
authors.forename: Maya Yu
authors.initials: MY
authors.lastname: Rubtsova
authors.affiliation: 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.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Majouga
authors.affiliation: European Molecular Biology Laboratory (EMBL), c/o DESY, Notkestrasse 85, Hamburg 22607, Germany.
authors.forename: Victor S
authors.initials: VS
authors.lastname: Lamzin
authors.affiliation: Chemistry Department, M.V. Lomonosov Moscow State University, Lenin Hills, 1, bld. 3, Moscow 119991, Russia.
authors.forename: Alexey M
authors.initials: AM
authors.lastname: Egorov
mesh_terms: D000813:Anilides / Q000737:chemistry; D020134:Catalytic Domain; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006860:Hydrogen Bonding; D007700:Kinetics; D062105:Molecular Docking Simulation; D010647:Phenyl Ethers / Q000737:chemistry; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives* / Q000737:chemistry; D065093:beta-Lactamase Inhibitors / Q000737:chemistry*; D001618:beta-Lactamases / Q000737:chemistry*
chemical_list: C000621534:4-((4-(2,4-dichloro)phenoxyphenyl)-4-carboxyphenyl)thiourea; D000813:Anilides; D029968:Escherichia coli Proteins; D010647:Phenyl Ethers; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases; C000621533:beta-lactamase TEM-171, E coli; D013890:Thiourea
keywords: Acylated phenoxyaniline; Molecular docking; TEM type β-lactamase; Thiourea; β-Lactamase inhibitors