Stage of action of naturally occurring andrographolides and their semisynthetic analogues against herpes simplex virus type 1 in vitro.

Andrographolide, an ENT-labdane diterpene, has been found to have activities against many viruses. Three free hydroxyls at C-3, C-14, and C-19 are involved in the activities. No stage of action has ever been explored. In this study, the naturally occurring compounds of andrographolide, 14-deoxy-11,12-didehydroandrographolide and 14-deoxyandrographolide, and eight semisynthetic analogues, modified at the three free OHs of andrographolide, were explored for their anti-HSV-1 activities. The concentrations that produced 80 % viable cells were used to test for both pre- and postinfections by using cytopathic effect reduction assays on Vero cell cultures. Three analogues, 14-acetyl-3,19-isopropylideneandrographolide, 14-acetylandrographolide, and 3,14,19-triacetylandrographolide, significantly exhibited preinfection step activity against the virus. For postinfection activity, only 3,19-isopropylideneandrographolide showed absolute inhibition of HSV-1 replication. Meanwhile, andrographolide exhibited slight inhibitory activities of 34.48 ± 6.93 % and 56.90 ± 2.65 % against HSV-1 for pre- and postinfection, respectively. The results confirm that the three hydroxyl moieties play a role in the anti-HSV-1 activity of andrographolide. From the study, it can be concluded that 14-acetyl analogues are good for blocking the viral entry, and 3,19-isopropylideneandrographolide, a cyclic dioxane analogue, is good for exerting postinfection anti-HSV-1 activity. © Georg Thieme Verlag KG Stuttgart · New York.