3-Trifluoromethylpyrazolones derived nucleosides: Synthesis and antiviral evaluation

Abstract

Dengue (DENV) viral infection is a global public health problem that infrequently develops life threatening diseases such as dengue hemorrhagic fever (DFS) and dengue shock syndrome (DSS). Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human corona virus with 38% fatality rate of infected patients. A series of 4-arylhydrazono-5-trifluoromethyl-pyrazolones, their ribofuranosyl, and 5'-deoxyribofuranosyl nucleosides were synthesized, geometry optimized using Density functional theory (DFT), and evaluated for their antiviral activity. 2-Nitrophenylhydrazonopyra-zolone derivative 5 showed significant activity against MERS-CoV (EC₅₀ = 4.6 μM). The nucleoside analog 8 showed moderate activity against DENV-2 (EC₅₀ = 10 μM), while the activity was abolished with the corresponding 5'-deoxyribonucleoside analogs. The identified hits in this study set this category of compounds for further future optimizations.

Keywords: Hydrazonopyrazolones; MERS-CoV; antiviral activity; dengue virus 2; nucleosides.