Determination of Non-Cytotoxic Antiviral Concentrations of Phosphoric Acid Derivatives and Nucleotide Base Analogues...

We studied cytotoxicity and the effect on cell viability in in vitro incubated mammalian embryonic cells of purine derivative aminophylline, indole derivative ergotamine tartrate, as well as the phosphoric acid derivatives 3-ethyl-2-hydroxy-2-oxa-1,4,2-oxazaphosphorinane (EHOOP) and α-ethyl-α-N-(hydroxyethylamino)methylphosphonic acid (ENHEAMPA) after inoculation of the cells with vaccine avipoxviral strain FK (fowl) with initial infectious titer 10⁶ CCID₅₀/ml for 24 or 48 h. The tested substances were applied for 24 or 48 h at concentrations of 10^-11-10^-2 mol/ml (aminophylline and ergotamine tartrate), as well as at 10^-11-10^-3 mol/ml (EHOOP and ENHEAMPA). In cell suspensions, the cytotoxic concentrations CC₅₀ (mol/ml) were determined corresponding to the death or alterations in half of the cells. They were 10^-3 and 10^-2 mol/ml for purine and indole analogues, respectively, whereas similar values for two phosphoric acid derivatives were 10^-5-10^-4 mol/ml. At low concentrations of the test substances, a decrease in cell viability was observed when exposure was prolonged from 24 to 48 h, which can be explained by pathogenic action of the inoculated virus. A decrease in cell viability was also observed when the concentration of the test agents was elevated, which can be explained by their intrinsic cytotoxic action at high concentrations. Overall, purine and indole analogues were less toxic for cultured mammalian cells than the test phosphoric acid derivatives. Purine analogue aminophylline had the lowest cytotoxicity, but exhibited maximum antiviral activity.