title: A potential andrographolide analogue against the replication of herpes simplex virus type 1 in vero cells.
abstract: Andrographolide (AD), and 14-deoxyandrographolide (DAD) isolated from Andrographis paniculata Nees, Acanthaceae, and 3,19-isopropylideneandrographolide (IPAD), a semi-synthetic compound of AD, were examined for anti-HSV-1 activity in vitro. The inhibitory effects of these compounds on viral entry and replication steps were determined using pre- and post-infection assays, respectively. All the three compounds exhibited less than 50% inhibitory act against viral entry. In the post-infection, IPAD displayed absolute inhibition, whereas AD and DAD gave moderate activity. IPAD was selected to determine for the stage of anti-replication by time-of-addition and time-of-removal assays. From the time of removal assay, IPAD activity began after 4 h and completed at 16 h post infection which corresponded to the early genes expression. Its ability to inhibit HSV-1 was confirmed by polymerase chain reaction and the expression of viral glycoproteins C and D by western blot analysis. No viral enveloped glycoproteins D and C expressions were found. IPAD exhibited anti-HSV-1 replication relating to the early step of replication. Structure-activity relationships of andrographolide against HSV-1 was proposed, it is the first report of this ent-labdane diterpene.
authors.affiliation: Pharmaceutical Chemistry, Khon Kaen University, Thailand.
authors.forename: Supawadee
authors.initials: S
authors.lastname: Seubsasana
authors.forename: Chamsai
authors.initials: C
authors.lastname: Pientong
authors.forename: Tipaya
authors.initials: T
authors.lastname: Ekalaksananan
authors.forename: Sasithorn
authors.initials: S
authors.lastname: Thongchai
authors.forename: Chantana
authors.initials: C
authors.lastname: Aromdee
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology*; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D004224:Diterpenes; C030419:andrographolide