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Abstract:
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.
