title: Inhibition of Mycobacterium tuberculosis strains H37Rv and MDR MS-115 by a new set of C5 modified pyrimidine nucleosides.
abstract: Two sets of pyrimidine nucleoside derivatives bearing extended alkyloxymethyl or alkyltriazolidomethyl substituents at position 5 of the nucleobase were synthesized and evaluated as potential antituberculosis agents. The impact of modifications at 3'- and 5'-positions of the carbohydrate moiety on the antimycobacterial activity and cytotoxicity was studied. The highest effect was shown for 5-dodecyloxymethyl-2'-deoxyuridine, 5-decyltriazolidomethyl-2'-deoxyuridine, and 5-dodecyltriazolidomethyl-2'-deoxycytidine. They effectively inhibited the growth of two Mycobacterium tuberculosis strains in vitro, laboratory H37Rv (MIC99=20, 10, and 20μg/mL, respectively) and clinical MDR MS-115 resistant to five top antituberculosis drugs (МIC99=50, 10, and 10μg/mL, respectively).
authors.affiliation: Engelhardt Institute of Molecular Biology RAS, 32 Vavilov Str., Moscow 119991, Russia.
authors.forename: Eduard R
authors.initials: ER
authors.lastname: Shmalenyuk
authors.forename: Larisa N
authors.initials: LN
authors.lastname: Chernousova
authors.forename: Inna L
authors.initials: IL
authors.lastname: Karpenko
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Kochetkov
authors.forename: Tatiana G
authors.initials: TG
authors.lastname: Smirnova
authors.forename: Sofia N
authors.initials: SN
authors.lastname: Andreevskaya
authors.forename: Alexander O
authors.initials: AO
authors.lastname: Chizhov
authors.forename: Olga V
authors.initials: OV
authors.lastname: Efremenkova
authors.forename: Ludmila A
authors.initials: LA
authors.lastname: Alexandrova
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D006801:Humans; D019169:Jurkat Cells; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification; D011741:Pyrimidine Nucleosides / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000995:Antitubercular Agents; D011741:Pyrimidine Nucleosides
keywords: Inhibitor; Mycobacterium tuberculosis; Nucleoside; Synthesis