Chemistry and anti-herpes simplex virus type 1 evaluation of 4-substituted-1 H -1,2,3-triazole-nitroxyl-linked hybrids

HSV disease is distributed worldwide. Anti-herpesvirus drugs are a problem in clinical settings, particularly in immunocompromised individuals undergoing herpes simplex virus type 1 infection. In this work, 4-substituted-1,2,3-1 H -1,2,3-triazole linked nitroxyl radical derived from TEMPOL were synthesized, and their ability to inhibit the in vitro replication of HSV-1 was evaluated. The nitroxide derivatives were characterized by infrared spectroscopy and elemental analysis, and three of them had their crystal structures determined by single-crystal X-ray diffraction. Four hybrid molecules showed important anti-HSV-1 activity with IC 50 values ranged from 0.80 to 1.32 µM. In particular, one of the nitroxide derivatives was more active than Acyclovir (IC 50 = 0.99 µM). All compounds tested were more selective inhibitors than the reference antiviral drug. Among them, two compounds were 4.5 (IC 50 0.80 µM; selectivity index CC 50 /IC 50 3886) and 7.7 times (IC 50 1.10 µM; selectivity index CC 50 /IC 50 6698) more selective than acyclovir (IC 50 0.99 µM; selectivity index CC 50 /IC 50 : 869). These nitroxide derivatives may be elected as leading compounds due to their antiherpetic activities and good selectivity. Graphic abstract