T7 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.

Palchykovska, L. G.; Vasylchenko, O. V.; Platonov, M. O.; Kostina, V. G.; Babkina, M. M.; Tarasov, O. A.; Starosyla, D. B.; Samijlenko, S. P.; Rybalko, S. L.; Deriabin, O. M.; Hovorun, D. M.

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-arylamides 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 μI. The compound 16 proved to be the most effective inhibitor of T7 RNAP with the IC50 value being 0.48 μI. 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 antimic- robial 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.

ANTIBACTERIAL agents; ANTIVIRAL agents; ANTINEOPLASTIC agents; CHEMICAL synthesis; RNA polymerases; BOVINE viral diarrhea virus

Biopolymers & Cell, 2012, Vol 28, Issue 6, p477

0233-7657

Academic Journal

10.7124/bc.00013A