Evaluation of antibacterial and antiviral activity of N-arylamides of 9-methyl and 9-methoxyphenazine-1-carboxylic acids – inhibitors of the phage T7 model transctiption

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.