Bogorad-Kobelska O. Interferonproducing, antiviral and cytokineinducing activity of diphenyl derivatives

Dissertation is devoted to the study of interferonproducing, antiviral and cytokineinducing activity of diphenyl derivatives, analogues of ukrainian antiviral drug amixine - 4,4'-bis-[2-(diethylamino)ethoxy] diphenyl dihydrochloride (compound 1) and 2-methoxycarbonyl-4-4'-bis-[2-(diethylamino)ethoxy] diphenyl dihydrochloride (compound 2) and the study of the relationship of these activities with the effect of tested compounds on the condition of the membranes of sensitive cells. It was found that interferonproducing properties of the compound 1 in the in vitro conditions don't concede those of amixine and its advantages are lower toxicity and greater range of interferonproducing concentrations. It was also found that compound 1 provides 100% protection against cytopathic effect of vesicular stomatitis virus in the application of preventive and therapeutic schemes as the drug amixine. Compound 2 delays the development of viral cytopathic effect only by 50%. The efficiency of compounds 1 and 2 was also shown against herpes simplex virus type I in the application of both schemes. It was established that the investigated compounds significantly increase the value of the electrophoretic mobility of murine T lymphocytes and influence the surface charge of the cells. Also, it was investigated the effect of diphenyl derivatives on the plasma membrane activation of the cells by their ability to increase membrane potential in the early stages of exposure to compounds. We found a stimulating effect of compound 1 on the mitochondrial activity of isolated rat hepatocytes in the early stages of their interaction with the cells. It is a testament of activation of the antiviral mitochondrial pathway which the final link is the production of type I interferon.