Inhibitory Effect of Pyridobenzoazoles on Orthomyxo-and Paramyxovirus Replication in vitro

Abstract

Among thirteen newly synthesized pyridobenzoazole derivatives which have been examined for anti-myxovirus and antiherpesvirus activities, three benzimidazoles emerged as potent anti-orthomyxo- or paramyxovirus compounds. 4-Cyano-2-benzamide-1-oxo-1,5-dihydropyrido[1,2a]benzimidazole (CBO-PB) showed broad antiviral activities against paramyxo-and orthomyxoviruses with EC50 of 0.1–2.0 μg ml−1, and 2-cyano-1-amino derivatives of CBO-PB (CCI-PB) were inhibitory to paramyxoviruses at 1.4–8.5 (μg ml−1 by a plaque reduction method. The third compound, 2-ethoxycarbonyl derivatives of CCI-PB was inhibitory only to respiratory syncytial virus (RSV) at 15–28 μg ml−1. Selectivity indexes of these 3 compounds for RSV in HeLa cells were 60, 86, and >13, respectively. All three compounds inhibited syncytium formation of RSV and Parainfluenzavirus (PFLUV) type 3 at comparable concentrations with EC50 for plaque formation. They inhibited antigen production of RSV and PFLUV at the concentrations that were 4 to 20-fold higher than those needed for plaque reduction, but they did not inhibit adsorption of virus to cells at all. All three compounds inhibited the growth of RSV in HeLa cells at 4-fold higher concentrations than their EC50 for plaque reduction.