Synthesis and in vitro assessment of triazole-based compounds as potential inhibitors of herpes simplex virus type 1

Abstract A library of novel 1,2,4-triazole derivatives fused with a pyrazine moiety (5a–5t) was successfully synthesized and evaluated for their therapeutic potential against HSV-I virus and oxidative stress. These compounds were assessed for anti-inflammatory, antioxidant, and anti-HSV activities, demonstrating encouraging biological profiles. In particular, compounds 5f and 5t exhibited markedly improved antiviral efficacy compared to the reference drug, Acyclovir. The antioxidant capacity was also notable, with compound 5b showing exceptional radical scavenging potential. To better understand the interaction at the molecular level, docking studies were conducted, indicating that these molecules could potentially inhibit HSV1, a key enzyme required for viral replication. Also, in silico testing was conducted for assessing drug-likeness, ADME characteristics, and stability of metabolism which was helpful for optimizing further lead designs. Although the experimental methods were accurately implemented, some human error such as timing during administration of the compounds, measuring, and other tasks may have slight variations which are not entirely avoidable. These possible blunders are, however, unlikely to change significantly the observed trends. Ultimately, the study emphasizes these new hybrids of triazole-pyrazine as potential precursors for the synthesis of powerful anti-HSV-I and possibly antibacterial medicines, which require more advanced pharmacological and clinical research.