The group of molecular tools for living system studies
The main research areas of the group include:
- design and synthesis of nucleotide modifications for fine tuning the properties of canonical and non-canonical secondary nucleic acids structures;
- development of nucleotide modifications suitable for antisense and RNAi technologies for regulating gene expression;
- synthesis and screening of probes/ligands for detecting and fine tuning physicochemical parameters of noncanonical secondary nucleic acids structures;
- development and study of the properties of metal-binding modifications within oligonucleotides;
- study of the physicochemical properties of modifications that arise in living organisms when exposed to mutagenic factors;
- design and synthesis of antiviral compounds.
|Andrey Aralov, Ph.D.||depart. dir.||Baruh238@mail.ru, |
New antiviral nucleoside derivatives for inhibiting the reproduction of varicella-zoster virus and tick-borne encephalitis virus (2018-11-30)
A series of analogues of potent antiviral perylene nucleoside dUY11 with methylthiomethyl (MTM), azidomethyl (AZM) and HO-C1-4-alkyl-1,2,3-triazol-1,4-diyl groups at 3`-O-position as well as the two products of copper-free alkyne-azide cycloaddition of the AZM derivative were prepared and evaluated against tick-borne encephalitis virus (TBEV). Four compounds showed EC50 ≤10 nM, thus appearing the most potent TBEV inhibitors to date. Moreover, these nucleosides have higher lipophilicity (clogP) and increased solubility in aq. DMSO vs. parent compound dUY11.
Phenoxazine scaffold is widely used to stabilize nucleic acid duplexes, as a part of fluorescent probes for the study of nucleic acid structure, recognition, and metabolism etc. We present the synthesis of phenoxazine-based nucleoside derivatives and their antiviral activity against a panel of structurally diverse viruses: enveloped DNA herpesviruses varicella zoster virus (VZV) and human cytomegalovirus, enveloped RNA tick-borne encephalitis virus (TBEV), and non-enveloped RNA enteroviruses. Studied compounds were effective against DNA and RNA viruses reproduction in cell culture. 3-(2’-Deoxy-β-D-ribofuranosyl)-1,3-diaza-2-oxophenoxazine proved to be a potent inhibitor of VZV replication with superior activity against wild type than thymidine kinase deficient strains (EC50 0.06 and 10 µM, respectively). This compound did not show cytotoxicity on all the studied cell lines. Several compounds showed promising activity against TBEV (EC50 0.35-0.91 µM), but the activity was accompanied with pronounced cytotoxicity. These compounds may be considered as a good starting point for further structure optimization as antiherpesviral or antiflaviviral compounds.
- (2018). 3′-O-Substituted 5-(perylen-3-ylethynyl)-2′-deoxyuridines as tick-borne encephalitis virus reproduction inhibitors. Eur J Med Chem 155, 77–83