Ò7 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

• Дата: 2012
• Автори: 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.
• Формат: Стаття
• Мова: English
• Опубліковано: Інститут молекулярної біології і генетики НАН України 2012
• Назва видання: Вiopolymers and Cell
• Теми: Bioorganic Chemistry
• Онлайн доступ: http://dspace.nbuv.gov.ua/handle/123456789/156855
• Назва журналу: Digital Library of Periodicals of National Academy of Sciences of Ukraine
• Цитувати: Ò7 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 / L.G. Palchykovska, O.V. Vasylchenko, M.O. Platonov, V.G. Kostina, M.M. Babkina, O.A. Tarasov, D.B. Starosyla, S.P. Samijlenko, S.L. Rybalko, O.M. Deriabin, D.M. Hovorun // Вiopolymers and Cell. — 2012. — Т. 28, № 6. — С. 477-485. — Бібліогр.: 32 назв. — англ., укр.

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.