2022  1,200
2021  1,540
2020  1,374
2019  1,023
2018  0,932
2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 55(2021) N 1 p. 143-153; DOI 10.1134/S002689332101012X Full Text

S.D. Negrya1*, M.V. Jasko1, D.A. Makarov1,4, P.N. Solyev1, I.L. Karpenko1, O.V. Shevchenko1, O.V. Chekhov1,3, A.A. Glukhova2, B.F. Vasilyeva2, T.A. Efimenko2, I.G. Sumarukova2, O.V. Efremenkova2, S.N. Kochetkov1, L.A. Alexandrova1

Glycol and Phosphate Depot Forms of 4- and/or 5-Modified Nucleosides Exhibiting Antibacterial Activity

1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
2Gause Institute of New Antibiotics, Moscow, 119021 Russia
3Moscow Institute of Physics and Technology, Dolgoprudny, Moscow oblast, 141700 Russia
4Mendeleev Russian University of Chemical Technology, Higher Chemical College, Russian Academy of Sciences, Moscow, 125047 Russia

Received - 2020-05-19; Revised - 2020-06-24; Accepted - 2020-06-25

Resistance developed to the majority of drugs used to treat infectious diseases warrants the design of new compounds effective against drug-resistant strains of pathogens. Recently, several groups of modified nucleosides have been synthesized and showed significant antibacterial activity in vitro, but their further studies were difficult to undertake because of their low solubility in aqueous solutions. Nevertheless, new compounds, well soluble in water-organic solutions, were synthesized and found to be more effective in inhibiting the growth of Gram-positive bacteria and mycobacteria. The water-soluble forms of modified nucleosides under study were assumed to be their depot forms. To check the assumption, the compounds were tested for hydrolysis in various media and their molecular docking was performed into the active center of the putative target, Mycobacterium tuberculosis flavin-dependent thymidylate synthase ThyX. Computer modelling showed that the water-soluble analogs do not act as ThyX inhibitors, supporting the assumption of their depot nature. The compounds were resistant to chemical hydrolysis but were hydrolyzed when incubated with porcine liver carboxylesterase, human serum, or Staphylococcus aureus 209P. The results demonstrate that the compounds are most likely depot forms of modified nucleosides.

antibiotic resistance, antiviral and antibacterial activities, modified nucleosides and nucleotides, prodrug, depot form of drug, Mycobacterium tuberculosis thymidylate synthase