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.
Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand. chaaro@kku.ac.th
Chantana
C
Aromdee
Supawadee
S
Suebsasana
Tipaya
T
Ekalaksananan
Chamsai
C
Pientong
Sasithorn
S
Thongchai
D035685:Andrographis / Q000737:chemistry*; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D014709:Vero Cells; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
C495626:14-deoxy-11,12-didehydroandrographolide; C114791:14-deoxyandrographolide; D000998:Antiviral Agents; D004224:Diterpenes; D010936:Plant Extracts; C030419:andrographolide