%0 Journal Article
%T Novel 5-substituted derivatives of 2¡¯-deoxy-6-azauridine with antibacterial activity
%J -
%D 2019
%R https://doi.org/10.1038/s41429-019-0158-z
%X The emergence of new drug-resistant strains of bacteria necessitates the development of principally new antibacterial agents. One of the novel classes of antibacterial agents is nucleoside analogs. We have developed a fast and simple one-pot method for preparation of ¦Á- and ¦Â-anomers of 5-modified 6-aza- and 2-thio-6-aza-2¡¯-deoxyuridine derivatives in high yields. 2-Thio derivatives demonstrated moderate activity against Mycobacterium smegmatis (MIC£¿=£¿0.2¨C0.8£¿mM), Staphylococcus aureus (MIC£¿=£¿0.03¨C0.9£¿mM) and some other Gram-positive bacteria. 2¡¯-Deoxy-2-thio-5-phenyl-6-azauridine (2b) effectively suppressed the growth of Gram-negative bacteria Pseudomonas aeruginosa ATCC 27853 (MIC£¿=£¿0.03£¿mM)¡ªthe one that causes diseases difficult to treat due to high resistance to antibiotics. 5¡¯-Monophosphates of compounds 2a, b and 3a, b were docked into a binding site of Mycobacterium tuberculosis flavin-dependent thymidylate synthase (ThyX) enzyme. The molecular modeling demonstrates the possibility of binding of the 5-modified 2-thio-6-aza-2¡¯-deoxyuridine 5¡¯-monophosphates within the active site of the enzyme and thereby inhibiting the growth of the bacteria
%U https://www.nature.com/articles/s41429-019-0158-z