title: 5-Arylaminouracil Derivatives: New Inhibitors of Mycobacterium tuberculosis.
abstract: Three series of 5-arylaminouracil derivatives, including 5-(phenylamino)uracils, 1-(4'-hydroxy-2'-cyclopenten-1'-yl)-5-(phenylamino)uracils, and 1,3-di-(4'-hydroxy-2'-cyclopenten-1'-yl)-5-(phenylamino)uracils, were synthesized and screened for potential antimicrobial activity. Most of compounds had a negative effect on the growth of the Mycobacterium tuberculosis H37Rv strain, with 100% inhibition observed at concentrations between 5 and 40 μg/mL. Of those, 1-(4'-hydroxy-2'-cyclopenten-1'-yl)-3-(4‴-hydroxy-2‴-cyclopenten-1‴-yl)-5-(4″-butyloxyphenylamino)uracil proved to be the most active among tested compounds against the M. tuberculosis multidrug-resistant strain MS-115 (MIC90 5 μg/mL). In addition, the thymidylate kinase of M. tuberculosis was evaluated as a possible enzymatic target.
authors.affiliation: Engelhardt Institute of Molecular Biology RAS, Vavilova 32, Moscow, 119991, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Matyugina
authors.affiliation: Department of Pharmaceutical & Toxicological Chemistry, Volgograd State Medical University, Pavshikh Bortsov Sq., 1, Volgograd, 400131, Russia.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Novikov
authors.affiliation: Department of Pharmaceutical & Toxicological Chemistry, Volgograd State Medical University, Pavshikh Bortsov Sq., 1, Volgograd, 400131, Russia.
authors.forename: Denis
authors.initials: D
authors.lastname: Babkov
authors.affiliation: Department of Pharmaceutical & Toxicological Chemistry, Volgograd State Medical University, Pavshikh Bortsov Sq., 1, Volgograd, 400131, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Ozerov
authors.affiliation: Central Tuberculosis Research Institute RAMS, Yauzskaya Alley 2, Moscow, 107564, Russia.
authors.forename: Larisa
authors.initials: L
authors.lastname: Chernousova
authors.affiliation: Central Tuberculosis Research Institute RAMS, Yauzskaya Alley 2, Moscow, 107564, Russia.
authors.forename: Sofia
authors.initials: S
authors.lastname: Andreevskaya
authors.affiliation: Central Tuberculosis Research Institute RAMS, Yauzskaya Alley 2, Moscow, 107564, Russia.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Smirnova
authors.affiliation: Engelhardt Institute of Molecular Biology RAS, Vavilova 32, Moscow, 119991, Russia.
authors.forename: Inna
authors.initials: I
authors.lastname: Karpenko
authors.affiliation: Zelinsky Institute of Organic Chemistry RAS, Leninsky pr. 47, Moscow, 119991, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Chizhov
authors.affiliation: Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA, 30322, USA.
authors.forename: Pravin
authors.initials: P
authors.lastname: Murthu
authors.affiliation: Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA, 30322, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lutz
authors.affiliation: Engelhardt Institute of Molecular Biology RAS, Vavilova 32, Moscow, 119991, Russia.
authors.forename: Sergei
authors.initials: S
authors.lastname: Kochetkov
authors.affiliation: Department of Chemistry & Biochemistry, University of Maryland, Baltimore, MD, 21250, USA.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Seley-Radtke
authors.affiliation: Engelhardt Institute of Molecular Biology RAS, Vavilova 32, Moscow, 119991, Russia.
authors.forename: Anastasia L
authors.initials: AL
authors.lastname: Khandazhinskaya
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D009703:Nucleoside-Phosphate Kinase / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D014376:Tuberculosis / Q000188:drug therapy; D014498:Uracil / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D014709:Vero Cells
chemical_list: D000995:Antitubercular Agents; D004791:Enzyme Inhibitors; D014498:Uracil; D009703:Nucleoside-Phosphate Kinase; C020093:dTMP kinase
keywords: Mycobacterium tuberculosis; carbocyclic nucleosides; uracil derivatives