Identification and evaluation of 4-anilinoquin(az)olines as potent inhibitors of both dengue virus (DENV) and Venezuelan equine encephalitis virus (VEEV)

There is an urgent need for novel strategies for the treatment of emerging arthropod-borne viral infections, including those caused by dengue virus (DENV) and Venezuelan equine encephalitis virus (VEEV). We prepared and screened focused libraries of 4-anilinoquinolines and 4-anilinoquinazolines for antiviral activity and identified three potent compounds. N-(2,5-dimethoxyphenyl)-6-(trifluoromethyl)quinolin-4-amine (10) inhibited DENV infection with an EC50 = 0.25 mu M, N-(3,4-dichlorophenyl)-6-(trifluoromethyl)quinolin-4-amine (27) inhibited VEEV with an EC50 = 0.50 mu M, while N-(3-ethynyl-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine (54) inhibited VEEV with an EC50 = 0.60 mu M. These series of compounds demonstrated nearly no toxicity with CC50 values greater than 10 mu M in all cases. These promising results provide a future prospective to develop a clinical compound against these emerging viral threats.

Automated summary

This study identified three potent compounds against dengue virus and Venezuelan equine encephalitis virus, all of which showed nearly no toxicity, providing promising prospects for the development of clinical compounds against these emerging viral threats.