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Natural stilbenoids isolated from grapevine exhibiting inhibitory effects against HIV-1 integrase and eukaryote MOS1 transposase in vitro activities.

Pflieger A, Waffo Teguo P, Papastamoulis Y, Chaignepain S, Subra F, Munir S, Delelis O, Lesbats P, Calmels C, Andreola ML, Merillon JM, Auge-Gouillou C, Parissi V - PLoS ONE (2013)

Bottom Line: Some of the molecules were found to be active against both proteins while others were specific for one of the two models.Comparison of the differential effects of the molecules suggested that the compounds could target specific intermediate nucleocomplexes of the reactions.Additionally E-pterostilbene was found active on the early lentiviral replication steps in lentiviruses transduced cells.

View Article: PubMed Central - PubMed

Affiliation: Université François Rabelais de Tours, EA 6306, UFR Sciences Pharmaceutiques, Parc Grandmont, Tours, France.

ABSTRACT
Polynucleotidyl transferases are enzymes involved in several DNA mobility mechanisms in prokaryotes and eukaryotes. Some of them such as retroviral integrases are crucial for pathogenous processes and are therefore good candidates for therapeutic approaches. To identify new therapeutic compounds and new tools for investigating the common functional features of these proteins, we addressed the inhibition properties of natural stilbenoids deriving from resveratrol on two models: the HIV-1 integrase and the eukaryote MOS-1 transposase. Two resveratrol dimers, leachianol F and G, were isolated for the first time in Vitis along with fourteen known stilbenoids: E-resveratrol, E-piceid, E-pterostilbene, E-piceatannol, (+)-E-ε-viniferin, E-ε-viniferinglucoside, E-scirpusin A, quadragularin A, ampelopsin A, pallidol, E-miyabenol C, E-vitisin B, hopeaphenol, and isohopeaphenol and were purified from stalks of Vitis vinifera (Vitaceae), and moracin M from stem bark of Milliciaexelsa (Moraceae). These compounds were tested in in vitro and in vivo assays reproducing the activity of both enzymes. Several molecules presented significant inhibition on both systems. Some of the molecules were found to be active against both proteins while others were specific for one of the two models. Comparison of the differential effects of the molecules suggested that the compounds could target specific intermediate nucleocomplexes of the reactions. Additionally E-pterostilbene was found active on the early lentiviral replication steps in lentiviruses transduced cells. Consequently, in addition to representing new original lead compounds for further modelling of new active agents against HIV-1 integrase, these molecules could be good tools for identifying such reaction intermediates in DNA mobility processes.

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General structure of resveratrol derivative stilbenes purified form Vitis vinifera grapevine.The compounds are divided into three families: monomers, dimers and higher order oligomers of the resveratrol motif. A list of the acronyms used in this work is reported in the figure.
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pone-0081184-g001: General structure of resveratrol derivative stilbenes purified form Vitis vinifera grapevine.The compounds are divided into three families: monomers, dimers and higher order oligomers of the resveratrol motif. A list of the acronyms used in this work is reported in the figure.

Mentions: The chemical structures of stilbenoids isolated and characterized from grapevine and Millicia excelsa are shown in figure 1. The primary objectives of the study were to investigate the isolation of new lead compounds deriving from resveratrol and to evaluate their in vitro activity in HIV-1 IN and MOS-1 transposase inhibitory assays for further modelling of new agents active against HIV-1 integrase.


Natural stilbenoids isolated from grapevine exhibiting inhibitory effects against HIV-1 integrase and eukaryote MOS1 transposase in vitro activities.

Pflieger A, Waffo Teguo P, Papastamoulis Y, Chaignepain S, Subra F, Munir S, Delelis O, Lesbats P, Calmels C, Andreola ML, Merillon JM, Auge-Gouillou C, Parissi V - PLoS ONE (2013)

General structure of resveratrol derivative stilbenes purified form Vitis vinifera grapevine.The compounds are divided into three families: monomers, dimers and higher order oligomers of the resveratrol motif. A list of the acronyms used in this work is reported in the figure.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3842960&req=5

pone-0081184-g001: General structure of resveratrol derivative stilbenes purified form Vitis vinifera grapevine.The compounds are divided into three families: monomers, dimers and higher order oligomers of the resveratrol motif. A list of the acronyms used in this work is reported in the figure.
Mentions: The chemical structures of stilbenoids isolated and characterized from grapevine and Millicia excelsa are shown in figure 1. The primary objectives of the study were to investigate the isolation of new lead compounds deriving from resveratrol and to evaluate their in vitro activity in HIV-1 IN and MOS-1 transposase inhibitory assays for further modelling of new agents active against HIV-1 integrase.

Bottom Line: Some of the molecules were found to be active against both proteins while others were specific for one of the two models.Comparison of the differential effects of the molecules suggested that the compounds could target specific intermediate nucleocomplexes of the reactions.Additionally E-pterostilbene was found active on the early lentiviral replication steps in lentiviruses transduced cells.

View Article: PubMed Central - PubMed

Affiliation: Université François Rabelais de Tours, EA 6306, UFR Sciences Pharmaceutiques, Parc Grandmont, Tours, France.

ABSTRACT
Polynucleotidyl transferases are enzymes involved in several DNA mobility mechanisms in prokaryotes and eukaryotes. Some of them such as retroviral integrases are crucial for pathogenous processes and are therefore good candidates for therapeutic approaches. To identify new therapeutic compounds and new tools for investigating the common functional features of these proteins, we addressed the inhibition properties of natural stilbenoids deriving from resveratrol on two models: the HIV-1 integrase and the eukaryote MOS-1 transposase. Two resveratrol dimers, leachianol F and G, were isolated for the first time in Vitis along with fourteen known stilbenoids: E-resveratrol, E-piceid, E-pterostilbene, E-piceatannol, (+)-E-ε-viniferin, E-ε-viniferinglucoside, E-scirpusin A, quadragularin A, ampelopsin A, pallidol, E-miyabenol C, E-vitisin B, hopeaphenol, and isohopeaphenol and were purified from stalks of Vitis vinifera (Vitaceae), and moracin M from stem bark of Milliciaexelsa (Moraceae). These compounds were tested in in vitro and in vivo assays reproducing the activity of both enzymes. Several molecules presented significant inhibition on both systems. Some of the molecules were found to be active against both proteins while others were specific for one of the two models. Comparison of the differential effects of the molecules suggested that the compounds could target specific intermediate nucleocomplexes of the reactions. Additionally E-pterostilbene was found active on the early lentiviral replication steps in lentiviruses transduced cells. Consequently, in addition to representing new original lead compounds for further modelling of new active agents against HIV-1 integrase, these molecules could be good tools for identifying such reaction intermediates in DNA mobility processes.

Show MeSH