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Prenylated phloroglucinols from Hypericum scruglii, an endemic species of Sardinia (Italy), as new dual HIV-1 inhibitors effective on HIV-1 replication

In a search for new potential multitarget anti-HIV compounds from natural products, we have identified in Hypericum scruglii, an endemic and exclusive species of Sardinia (Italy), a potent plant lead. The phytochemical study of the hydroalcoholic extract obtained from its leaves led to the isolation...

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Autores principales: Sanna, Cinzia, Scognamiglio, Monica, Fiorentino, Antonio, Corona, Angela, Graziani, Vittoria, Caredda, Alessia, Cortis, Pierluigi, Montisci, Mariofilippo, Ceresola, Elisa Rita, Canducci, Filippo, Poli, Ferruccio, Tramontano, Enzo, Esposito, Francesca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877874/
https://www.ncbi.nlm.nih.gov/pubmed/29601601
http://dx.doi.org/10.1371/journal.pone.0195168
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author Sanna, Cinzia
Scognamiglio, Monica
Fiorentino, Antonio
Corona, Angela
Graziani, Vittoria
Caredda, Alessia
Cortis, Pierluigi
Montisci, Mariofilippo
Ceresola, Elisa Rita
Canducci, Filippo
Poli, Ferruccio
Tramontano, Enzo
Esposito, Francesca
author_facet Sanna, Cinzia
Scognamiglio, Monica
Fiorentino, Antonio
Corona, Angela
Graziani, Vittoria
Caredda, Alessia
Cortis, Pierluigi
Montisci, Mariofilippo
Ceresola, Elisa Rita
Canducci, Filippo
Poli, Ferruccio
Tramontano, Enzo
Esposito, Francesca
author_sort Sanna, Cinzia
collection PubMed
description In a search for new potential multitarget anti-HIV compounds from natural products, we have identified in Hypericum scruglii, an endemic and exclusive species of Sardinia (Italy), a potent plant lead. The phytochemical study of the hydroalcoholic extract obtained from its leaves led to the isolation of its most abundant secondary metabolites, belonging to different chemical classes. In particular, three phloroglucinols derivatives were identified, confirming their significance as chemotaxonomic markers of the Hypericum genus. Among them, the 3-(13-hydroxygeranyl)-1-(2'-methylbutanoyl)phloroglucinol was reported here for the first time. All six isolated compounds have been evaluated firstly for the inhibition of both Human Immunodeficiency Virus type 1 (HIV-1) Reverse Transcriptase (RT)-associated DNA Polymerase (RDDP) and Ribonuclease H (RNase H) activities, for the inhibition of HIV-1 integrase (IN) in biochemical assays, and also for their effect on viral replication. Among the isolated metabolites, three phloroglucinol derivatives and quercitrin were effective on both RT-associated RDDP and RNase H activities in biochemical assays. The same active compounds affected also HIV-1 IN strand transfer function, suggesting the involvement of the RNase H active site. Furthermore, phloroglucinols compounds, included the newly identified compound, were able to inhibit the HIV-1 replication in cell based assays.
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spelling pubmed-58778742018-04-13 Prenylated phloroglucinols from Hypericum scruglii, an endemic species of Sardinia (Italy), as new dual HIV-1 inhibitors effective on HIV-1 replication Sanna, Cinzia Scognamiglio, Monica Fiorentino, Antonio Corona, Angela Graziani, Vittoria Caredda, Alessia Cortis, Pierluigi Montisci, Mariofilippo Ceresola, Elisa Rita Canducci, Filippo Poli, Ferruccio Tramontano, Enzo Esposito, Francesca PLoS One Research Article In a search for new potential multitarget anti-HIV compounds from natural products, we have identified in Hypericum scruglii, an endemic and exclusive species of Sardinia (Italy), a potent plant lead. The phytochemical study of the hydroalcoholic extract obtained from its leaves led to the isolation of its most abundant secondary metabolites, belonging to different chemical classes. In particular, three phloroglucinols derivatives were identified, confirming their significance as chemotaxonomic markers of the Hypericum genus. Among them, the 3-(13-hydroxygeranyl)-1-(2'-methylbutanoyl)phloroglucinol was reported here for the first time. All six isolated compounds have been evaluated firstly for the inhibition of both Human Immunodeficiency Virus type 1 (HIV-1) Reverse Transcriptase (RT)-associated DNA Polymerase (RDDP) and Ribonuclease H (RNase H) activities, for the inhibition of HIV-1 integrase (IN) in biochemical assays, and also for their effect on viral replication. Among the isolated metabolites, three phloroglucinol derivatives and quercitrin were effective on both RT-associated RDDP and RNase H activities in biochemical assays. The same active compounds affected also HIV-1 IN strand transfer function, suggesting the involvement of the RNase H active site. Furthermore, phloroglucinols compounds, included the newly identified compound, were able to inhibit the HIV-1 replication in cell based assays. Public Library of Science 2018-03-30 /pmc/articles/PMC5877874/ /pubmed/29601601 http://dx.doi.org/10.1371/journal.pone.0195168 Text en © 2018 Sanna et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Sanna, Cinzia
Scognamiglio, Monica
Fiorentino, Antonio
Corona, Angela
Graziani, Vittoria
Caredda, Alessia
Cortis, Pierluigi
Montisci, Mariofilippo
Ceresola, Elisa Rita
Canducci, Filippo
Poli, Ferruccio
Tramontano, Enzo
Esposito, Francesca
Prenylated phloroglucinols from Hypericum scruglii, an endemic species of Sardinia (Italy), as new dual HIV-1 inhibitors effective on HIV-1 replication
title Prenylated phloroglucinols from Hypericum scruglii, an endemic species of Sardinia (Italy), as new dual HIV-1 inhibitors effective on HIV-1 replication
title_full Prenylated phloroglucinols from Hypericum scruglii, an endemic species of Sardinia (Italy), as new dual HIV-1 inhibitors effective on HIV-1 replication
title_fullStr Prenylated phloroglucinols from Hypericum scruglii, an endemic species of Sardinia (Italy), as new dual HIV-1 inhibitors effective on HIV-1 replication
title_full_unstemmed Prenylated phloroglucinols from Hypericum scruglii, an endemic species of Sardinia (Italy), as new dual HIV-1 inhibitors effective on HIV-1 replication
title_short Prenylated phloroglucinols from Hypericum scruglii, an endemic species of Sardinia (Italy), as new dual HIV-1 inhibitors effective on HIV-1 replication
title_sort prenylated phloroglucinols from hypericum scruglii, an endemic species of sardinia (italy), as new dual hiv-1 inhibitors effective on hiv-1 replication
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877874/
https://www.ncbi.nlm.nih.gov/pubmed/29601601
http://dx.doi.org/10.1371/journal.pone.0195168
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