Stage of Action of Naturally Occurring Andrographolides and Their Semisynthetic Analogues against Herpes Simplex Virus Type 1in Vitro

Abstract

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.

Synergistic effects of acyclovir and 3, 19- isopropylideneandrographolide on herpes simplex virus wild types and drug-resistant strains

“…Andrographolide (Androg) is a bioactive ent- labdane diterpene isolated from Andrographis paniculata Nees, Acanthaceae and has been used to treat various diseases traditionally in the Southeast Asian countries, India and China. The pure form of Androg and its derivatives were isolated and already characterized [ 7 ]. In our recent studies, 3, 19-isopropylideneandrographolide (IPAD), an analogue of Androg, was found to exert an absolute inhibitory effect on HSV-1 post-infection at the concentration of 11.96 μM [ 7 , 8 ].…”

“…The pure form of Androg and its derivatives were isolated and already characterized [ 7 ]. In our recent studies, 3, 19-isopropylideneandrographolide (IPAD), an analogue of Androg, was found to exert an absolute inhibitory effect on HSV-1 post-infection at the concentration of 11.96 μM [ 7 , 8 ]. IPAD affects the early steps of DNA replication in HSV-1.…”

“…IPAD affects the early steps of DNA replication in HSV-1. Its action influences viral DNA synthesis and expression of gC and gD [ 7 ].…”

Activity of Andrographolide and Its Derivatives on HPV16 Pseudovirus Infection and Viral Oncogene Expression in Cervical Carcinoma Cells

“…Another study has demonstrated that 14-DDA isolated from A. paniculata shows virucidal activity against herpes simplex virus 1 (HSV-1) (25). Our previous study also found that 3 andrographolide analogues, namely 14-acetyl-3,19-isopropylideneandrographolide, 14-acetylandrographolide, and 3,14,19-triacetylandrographolide, significantly exhibit preinfection step activity against HSV-1 and concluded that 14-acetyl analogues are good for blocking viral entry (19). Several natural compounds have been reported to have effects on the early step of HPV infection.…”

“…The preparation and structure of A. paniculata compounds have been described previously (19). Andrographolide (Androg), 14-DDA, and IPAD were dissolved in dimethyl sulfoxide (DMSO; Amresco, Solon, OH) for stock solutions (2 mg/mL) and stored at -20 C. The stock solutions were freshly diluted to the indicated concentrations with culture medium before using in experiments.…”