37077-80-8Relevant articles and documents
Synthesis of 1,2,3-triazolyl nucleoside analogues and their antiviral activity
Andreeva, Olga V.,Garifullin, Bulat F.,Zarubaev, Vladimir V.,Slita, Alexander V.,Yesaulkova, Iana L.,Saifina, Liliya F.,Shulaeva, Marina M.,Belenok, Maya G.,Semenov, Vyacheslav E.,Kataev, Vladimir E.
, p. 473 - 490 (2020/09/22)
Abstract: Based on the fact that a search for influenza antivirals among nucleoside analogues has drawn very little attention of chemists, the present study reports the synthesis of a series of 1,2,3-triazolyl nucleoside analogues in which a pyrimidine fragment is attached to the ribofuranosyl-1,2,3-triazol-4-yl moiety by a polymethylene linker of variable length. Target compounds were prepared by the Cu alkyne-azide cycloaddition (CuAAC) reaction. Derivatives of uracil, 6-methyluracil, 3,6-dimethyluracil, thymine and quinazolin-2,4-dione with ω-alkyne substituent at the N1 (or N5) atom and azido 2,3,5-tri-O-acetyl-D-β-ribofuranoside were used as components of the CuAAC reaction. All compounds synthesized were evaluated for antiviral activity against influenza virus A/PR/8/34/(H1N1) and coxsackievirus B3. The best values of IC50 (inhibiting concentration) and SI (selectivity index) were demonstrated by the lead compound 4i in which the 1,2,3-triazolylribofuranosyl fragment is attached to the N1 atom of the quinazoline-2,4-dione moiety via a butylene linker (IC50 = 30?μM, SI = 24) and compound 8n in which the 1,2,3-triazolylribofuranosyl fragment is attached directly to the N5 atom of the 6-methyluracil moiety (IC50 = 15?μM, SI = 5). According to theoretical calculations, the antiviral activity of the 1,2,3-triazolyl nucleoside analogues 4i and 8n against H1N1 (A/PR/8/34) influenza virus can be explained by their influence on the functioning of the polymerase acidic protein (PA) of RNA-dependent RNA polymerase (RdRP). Graphic abstract: [Figure not available: see fulltext.]
Synthesis of novel 1,2,3-triazolyl nucleoside analogues bearing uracil, 6-methyluracil, 3,6-dimethyluracil, thymine, and quinazoline-2,4-dione moieties
Andreeva, Olga V.,Belenok, Maya G.,Saifina, Liliya F.,Shulaeva, Marina M.,Dobrynin, Alexey B.,Sharipova, Radmila R.,Voloshina, Alexandra D.,Saifina, Alina F.,Gubaidullin, Aidar T.,Khairutdinov, Bulat I.,Zuev, Yuriy F.,Semenov, Vyacheslav E.,Kataev, Vladimir E.
supporting information, (2019/11/05)
A series of novel 1,2,3-triazolyl nucleoside analogues was synthesized via the CuAAC reaction of N1-alkynyl uracil, 6-methyluracil, 3,6-dimethyl uracil, thymine and quinazolin-2,4-dione with protected azido β-D-ribofuranose. The obtained compounds differ in both the nature of the pyrimidine-2,4-dione fragment and the length of the polymethylene linker connecting it with the β-D-ribofuranosyl-1,2,3-triazol-4-yl moiety. The 1,2,3-triazolyl nucleoside analogues were evaluated for their cytotoxicity in vitro.
Anaerobic 5-Hydroxybenzimidazole Formation from Aminoimidazole Ribotide: An Unanticipated Intersection of Thiamin and Vitamin B12 Biosynthesis
Mehta, Angad P.,Abdelwahed, Sameh H.,Fenwick, Michael K.,Hazra, Amrita B.,Taga, Michiko E.,Zhang, Yang,Ealick, Steven E.,Begley, Tadhg P.
supporting information, p. 10444 - 10447 (2015/09/28)
Comparative genomics of the bacterial thiamin pyrimidine synthase (thiC) revealed a paralogue of thiC (bzaF) clustered with anaerobic vitamin B12 biosynthetic genes. Here we demonstrate that BzaF is a radical S-adenosylmethionine enzyme that catalyzes the remarkable conversion of aminoimidazole ribotide (AIR) to 5-hydroxybenzimidazole (5-HBI). We identify the origin of key product atoms and propose a reaction mechanism. These studies represent the first step in solving a long-standing problem in anaerobic vitamin B12 assembly and reveal an unanticipated intersection of thiamin and vitamin B12 biosynthesis.