Antiretroviral activity of two polyisoprenylated acylphloroglucinols, 7-epi-nemorosone and plukenetione A, isolated from Caribbean propolis.

Abstract

OBJECTIVES:

Polyisoprenylated acylphloroglucinols have recently emerged as antitumoral agents. This study aims at elucidating the antiretroviral activity of two such compounds which were isolated from Caribbean propolis: 7-epi-nemorosone and plukenetione A, the structure of which is based on an adamantane moiety. Plukenetione A is for the first time shown to have antiretroviral activity.

MATERIAL AND METHODS:

The isolation of both small molecules was carried out using RP-HPLC. Their antiretroviral activity was studied based on lentiviral particles produced in HEK293T cells from the SIV-based vector VLDBH; their cytotoxicity was monitored by MTT proliferation assay. The antiviral activity of 7-epi-nemorosone was studied in CEMx174-SEAP infected with the HIV-1-strain pNL4.3wt. Reverse transcriptase inhibition was determined by a standard two-step RT-PCR using MMLV RT.

RESULTS:

7-epi-nemorosone and plukenetione A were found to be potent antilentiviral agents in the employed system, inhibiting viral infection at concentrations below 1 µM/2 µM, respectively. Whereas 7-epi-nemorosone was not able to inhibit the reverse transcriptase in vitro (IC50 > 25 µM), plukenetione A effectively inhibited its enzymatic activity at an IC50 of 1.75 µM.

CONCLUSIONS:

Despite 7-epi-nemorosone and plukenetione A sharing some structural core elements, the mechanism of action involved in their antiretroviral activity seems to be different. We propose that 7-epi-nemorosone inhibits the viral replication by interrupting the Akt/PKB signaling cascade, as was demonstrated previously in various cell lines. Since plukenetione A effectively inhibits the enzymatic activity of MMLV reverse transcriptase at concentrations that show antilentiviral activity, we suggest that this small molecule acts by interfering with the enzyme's catalytic site.

• Authors: D Díaz-Carballo, K Ueberla, V Kleff, S Ergun, S Malak, M Freistuehler, S Somogyi, C Kücherer, W Bardenheuer, D Strumberg
• Journal: International journal of clinical pharmacology and therapeutics (Int J Clin Pharmacol Ther) Vol. 48 Issue 10 Pg. 670-7 (Oct 2010) ISSN: 0946-1965 [Print] Germany
• PMID: 20875373 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Benzophenones
• Polycyclic Compounds
• nemorosone
• plukenetione A
• Propolis

Topics

• Antiviral Agents (pharmacology)
• Benzophenones (chemistry, pharmacology)
• Caribbean Region
• Cells, Cultured
• HIV-1 (drug effects)
• Humans
• Lentivirus (drug effects)
• Polycyclic Compounds (chemistry, pharmacology)
• Propolis (chemistry)