New simplex Type 1 lytic infection pyridine system derivative as a novel goal against Herpes

Abstract

The pyridine system derivatives have been studied as antiviral drug new models against HIV infection using bioisosterism as a powerful tool. In the last decades, the number of this work, thienopyridine derivatives were evaluated as an HSV-1 inhibitor to since the elevated number of acyclovir resistance in immunocompromised patients could promote a continuous viral pool increase and disease recurrence. In these substances, thienopyridine derivative with radical nitrate in para position (109) was able to inhibit 99% of HSV-1 replication in Vero cells with EC ₅₀ value of 100 pM, and SI value three times higher than acyclovir. In kinetic enzymatic assay this substance was also able to inhibit about 50% of HSV-1 DNA polymerase but in a non-competitive mechanism a new synergic system to control herpes infections. Preliminary in vivo model studies revealed that substance 109 is toxic when administered in 300 g/mL concentrations. In this work, we concluded that thienopyridine derivatives can be considered a promising new anti-HSV-1 drug and can be used for clinical testing.