New low molecular weight heterocyclic compounds with antiviral activity

Development of an effective antiviral drug is typically followed by expansion of the successful strategy with numerous chemical variations of compounds providing improvements in parameters including affinity, solubility, lipophilicity, pharmacology, toxicity, drug resistance profiles etc. The aim of this study was to investigate the antiviral properties of newly synthesized fluorine-, chlorine-, and bromine-containing heterocyclic compounds against adeno-, herpes-, and influenza viruses. Cytotoxicity and antiviral efficacy of compounds was determined using a tetrazolium-based colorimetric and yield reduction assays, respectively. It should be noted that viability results were dependent on the type of used cells (CC₅₀ value of compounds was in range 167-2570 µg/mL). However, compound 3-(difluoromethyl)-2H-benzo[4,5]imidazole[1,2-b][1,2,6]thiadiazine-4-carbonitrile 1,1-dioxide (1792) was significantly toxic for cells of human laryngeal carcinoma which may indicate its antitumor properties. It was found that compound 5,7-dimethyl-4,7-dihydropyrazolo[4,3-e][1,2,4]thiadiazine1,1-dioxide with 3-(difluoromethyl), 3-(dichloromethyl) or 3-(trichloromethyl) substituents (1784, 1779 and 1781, respectively) inhibited HAdV-2 development of virus cytopathic effect on cells up to 49% and decreased infectious titer of virus obtained de novo by 1-5 log₁₀TCID₅₀/mL. Instead, significant antiinfluenza activity was observed for compound 1792, that decreased IAV reproduction up to 73%. Whereas for herpetic infection, antiviral effect of compounds was not detected, as the reduction of infectious titer did not exceed 0.6 log₁₀TCID₅₀/mL. Obtained data indicate that synthesized compounds may be promising antiviral agent. Furthermore, we showed that incorporation of the fluorine or chlorine atoms in molecule of compound significantly impact on its cytotoxicity and antiviral potency.