Biopolym. Cell. 2012; 28(6):477-485.
http://dx.doi.org/10.7124/bc.00013A
Bioorganic Chemistry
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
1Palchykovska L. G., 1Vasylchenko O. V., 1Platonov M. O., 1Kostina V. G., 2Babkina M. M., 2Tarasov O. A., 3Starosyla D. B., 1Samijlenko S. P., 3Rybalko S. L., 2Deriabin O. M., 1Hovorun D. M.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Institute of Veterinary Medicine, NAAS of Ukraine
    30, Donetska Str., Kyiv, Ukraine, 03151
  3. Gromashevsky L.V. Institute of Epidemiology and Infection Diseases, AMS of Ukraine
    5, Amosova Str., Kyiv, Ukraine, 03038

Abstract

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 concentrations of 0.48–61 µM. The compound 16 proved to be the most effective inhibitor of T7 RNAP with the IC50 value being 0.48 µM. 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.
Keywords: N-arylamides 9-substituted PCA, model system of the DNA-dependent RNA-polymerase of phage T7, antibacterial activity, antiviral activity
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