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This paper presents the results of synthesis and study of cytotoxicity and the anti-adenoviral activity of new N4-derivatives of 6-azacytidine and its α-L-glycopyranosyl analogues obtained by the simplified one-pot version of the silyl condensation method. The resulting acylated 4-methylmercapto-1,2,4-triazin-3(2Н)-one glycosides then underwent the amination and/or ammonolysis to provide 6-azacytidine glycoside analogues (2-6, 12, 15, 17) and compounds with modifications at both base and sugar fragments (11, 15). The evaluation of cytotoxicity and antiviral activity of new compounds against AdV5 showed high selectivity indexes for N4-methyl-6-azacytidine (2) and N,O-tetraacetyl-6-azacytidine (8). High anti-adenoviral activity of N4-methyl-6-azacytidine as well as very low cytotoxicity may suggest its further investigation as potential compound for the therapy of AdV infection.

Aim. To investigate influence of the Deschampsia caespitosa L. and Calamagrostis epogeios L. herbal extract (HE) and its main components – quercetin derivatives – on the DNA and RNA synthesis; to per- form comparative analysis of their antiviral activities. Methods. The model transcription system of bacteriophage T7 (RNAP T7) and polymerase chain reaction (PCR) were used as test systems. For antiviral studies there were employed models of influenzal and herpetic infections and hepatitis C. Results. It was shown, that HE, its major component 7, 3'-dimetoxyquercetin (DMQ) its minor component 5,7,3',4'-tetrametho- xyqeercetin (TMQ) effectively inhibited the RNA synthesis in the RNAP T7 system with the corresponding values of IC50 – 0.07, 4 and 1 µg/ml. Minimal concentrations of the agents IC90, completely inhibiting PCR, were – 8, 30 and 40 µg/ml for HE, TMQ and DMQ, accordingly. All the studied preparations revealed high multiple antiviral activities against the RNA- and DNA-containing viruses. Conclusions. Antiviral activity of the herbal extract is likely determined by the combined action of its components, TMQ and DMQ including. Bearing in mind multi-target profile of quercetin derivatives, an assumption may be made, that antiviral mechanism of the agents studied consists in blocking of enzymatic systems of the RNA and DNA synthesis

To enlarge a spectrum of biologically active compounds in the series of the 1,2,4-triazino[5,6-b] [1,4]benzothiazine (1,2,4-TBT) derivatives and reveal among them efficient inhibitors of RNA synthesis Methods. The methods of structure optimization of the 3-oxo-1,2,4-TBT by fragment-oriented substitution, the molecular doking of new structures in a virtual target, the rational chemical synthesis of the theoretically predicted compounds and their testing in the system of transcription in vitro. Results. The series of 1,2,4-TBT derivatives with substituents in the benzene and triazine cycles of a base molecule were synthesized. The testing of synthesized compounds in the in vitro transcription system directed by T7 RNA polymerase revealed the structure-and concentration dependent inhibition of the RNA synthesis by some of these compounds. The experimental and virtual screening data for all investigated compounds have a good correlation. It was found that most effective derivative is the 3-oxo-8-butyl-1,2,4-TBT which completely inhibited transcription at the concentration of 6 mg/ml. Conclusions. The biotesting results allow us to assume that the inhibition of RNA synthesis is caused by binding of the 3-oxo-8-butyl-1,2,4-TBT to both free RNA polymerase molecules and those including in a transcriptional complex with DNA.

Aim. Search for compounds with antibacterial and antiviral properties among N-arylamides of 9-substituted phenazine-1-carboxylic acids (PCA), inhibitors of the RNA synthesis. Methods. Influence of N-aryl-amides on the RNA synthesis was tested in vitro in the model system of the DNA-dependent RNA polymerase of phage T7 (T7 RNAP). Antimicrobial activities of the N-arylamides against bacteria Erysipelothrix rhusiopathiae VR-2 var. IVM, Klebsiella spp. and Escherichia coli ATCC25922 were investigated by the method of two-fold dilution in a liquid medium. Antiviral effects against Bovine Viral Diarrhea Virus (BVDV) and cytotoxicity of the N-arylamides were evaluated using Madin-Darby bovine kidney (MDBK) cells. Results. Twenty N-arylamides appeared to be efficacious inhibitors of the RNA synthesis at concent- rations of 0.48–61 µМ. The compound 16 proved to be the most effective inhibitor of T7 RNAP with the IC50 value being 0.48 µМ. Fourteen N-arylamides demonstrated antibacterial properties against gram positive and gram negative bacteria at the 0.1–10 µg/ml concentrations. A number of the N-arylamides revealed a multiplicity of their antimicrobial actions: 7 compounds against two bacteria and two compounds, 2 and 3, against three bacteria investigated. N-arylamides 16 and 26 showed high inhibitory activity as to BVDV with the IC50 values 0.43 and 0.88 µg/ml and SI values 160 and 10 correspondingly. Conclusions. The obtained data evidence that the most likely targets of the N-arylamides 9-substituted PCA in bacteria and viruses are their RNA synthesizing complexes