Antiviral activities against herpes simplex virus type 1 by HPH derivatives and their structure–activity relationships

The compound named Histidine–pyridine–histidine (HPH) is an oxygen-activating ligand derived from the structure of bleomycin. We synthesized HPH derivatives, namely HPH-1 to -8, and investigated their antiviral activities against herpes simplex virus type 1. HPH-8 showed potent antiviral activity with an EC50 of 15 μM, and relatively high cytotoxicity with a CC50 of 37 μM. In contrast, HPH-4 indicated a weaker antiviral activity with an EC50 of 79 μM, but exhibited a far more less cytotoxicity (CC50 500 μM). Other HPH derivatives showed no effects against antiviral activities and cytotoxicities.