ANTIVIRAL ACTIVITY of NOVEL indole-containing CONDENSED tetracyclic COMPOUNDS

 

V. S. Tashuta1, Z. S. Klestova2, A. K. Voronina3, S. Dgebuadze4

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1Institute of Veterinary Medicine Academy of Agricultural Sciences, Donetska st., 30,

Kyiv, 03151, Ukraine

2State Scientific Control Institute of Biotechnology and strains, Donetska st, 30,

Kyiv, 03151, Ukraine

3Institute of Pharmacology and Toxicology NAMS, Eugène Pottier st., 14,

Kyiv, 03680, Ukraine

4Georgian Technical University, Kostava st., 77, Tbilisi, 0175, Georgia

The article presents the results of determination in vitro of antiviral activity of 50 novel indole-containing condensed tetracyclic compounds relatively Aujeszky's disease virus and transmissible gastroenteritis in model of continuous animal cell cultures (BHK-21 SKEV, SK-6). 5 schemes have been applied to carry compounds in cell monolayers which were cultured in 96-well plates. Cell monolayer has been treated with studied chemicals for 24 hours before, during and in 1.5 hours after adsorption of the virus on the cells. Also in the two schemes before carrying virus in cell monolayer it was mixed with a chemical compound during 1 hour. Selecting of chemical compounds was carried out on the basis of inhibition of virus-induced cytopathic effect in animal cell cultures. Condition for the presence of cell-induced cytopathic effect was observed every 24 hours in the inverted microscope, and after 96 hours the titer of infectious activity of virus was determined in test and control wells. It was determined that some indole derivatives act only in certain schemes of application or cell cultures and other — in different. The infectivity of the Aujeszky’s disease virus decreased (ranging from 1.51±0.06 to 5.3±0.09 lg TCD50/cm3) in the application of 21 indole derivatives, 13 of which reduced the virus titer in two or more cell cultures, indicating the authentic biological effect. It was established that 33 indole-containing compounds reduced the titer of TGE virus (in the range of 1.52±0.08 to 5.16±0.07 lg TCD50/cm3), 12 of which — in two or more cell cultures. 18 indole derivatives possess the ability to reduce the infectious activity as Aujeszky's disease virus and the TGE virus, which gives a base for further clinical trials as a candidate antiviral drug.

Keywords:MPC (maximum permissible concentration), CPE (сytopathic effect), antiviral activity, indole-containing compounds, Aujeszky's disease, transmissible gastroenteritis

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