Chemical Characterization and Anti-HIV-1 Activity Assessment of Iridoids and Flavonols from Scrophularia trifoliata

Abstract

Plants are the everlasting source of a wide spectrum of specialized metabolites, characterized by wide variability in term of chemical structures and different biological properties such antiviral activity. In the search for novel antiviral agents against Human Immunodeficiency Virus type 1 (HIV-1) from plants, the phytochemical investigation of Scrophularia trifoliata L. led us to isolate and characterize four flavonols glycosides along with nine iridoid glycosides, two of them, 5 and 13, described for the first time. In the present study, we investigated, for the first time, the contents of a methanol extract of S. trifoliata leaves, in order to explore the potential antiviral activity against HIV-1. The antiviral activity was evaluated in biochemical assays for the inhibition of HIV-1Reverse Transcriptase (RT)-associated Ribonuclease H (RNase H) activity and HIV-1 Integrase (IN). Three isolated flavonoids, rutin, kaempferol-7-O-rhamnosyl-3-O-glucopyranoside, and kaempferol-3-O-glucopyranoside, 8–10, inhibited specifically the HIV-1 IN activity at submicromolar concentration, with the latter being the most potent, showing an IC50 value of 24 nM.

In Vitro Anti-HIV-1 Reverse Transcriptase and Integrase Properties of Punica granatum L. Leaves, Bark, and Peel Extracts and Their Main Compounds

“…However, despite the relatively large amount of literature on pomegranate fruits (juice and peel), much less information is available regarding the other organs. In our search for anti-HIV-1 agents from plants [28,[34][35][36][37][38][39], we firstly tested the ethanolic extracts obtained from the leaves (PGL), bark (PGB), and peels (PGP) of P. granatum from Sardinia for their ability to inhibit the RT-associated RNase H activity. This is regarded as an attractive and innovative target, since even though the majority of anti-AIDS molecules available for therapy are represented by RT inhibitors, all of them inhibit its associated DNA polymerase activity.…”

HIV-1 Integrase Inhibition Activity by Spiroketals Derived from Plagius flosculosus, an Endemic Plant of Sardinia (Italy) and Corsica (France)

“…Given the structural homologies between HIV-1 IN and the RNase H catalytic core, a great number of plant extracts active on IN was found to be capable of affecting HIV-1 RNase H activity [ 22 , 23 , 32 , 33 ]. Therefore, with the aim to investigate whether P. flosculosus extracts exert dual inhibition on both HIV-1 enzymes, we evaluated their effect on HIV-1 RNase H function.…”

“…In this context, in an effort to discover natural compounds able to block the HIV-1 infection, we focused our attention on the endemic flora of Sardinia Island (Italy), known to be an important source of bioactive molecules [ 21 ]. Compounds obtained from Sardinian endemic plants were found able to inhibit HIV-1 replication, blocking the HIV-1 IN LEDGF-dependent activity, or the IN–IN interaction and the RNase H function [ 22 , 23 ].…”

Promising inhibition of diabetes-related enzymes and antioxidant properties of Ptilostemon casabonae leaves extract

“…Even though many Sardinian endemic species have been reported as source of unique and structurally diverse compounds endowed with promising biological activities 3 , 4 , the majority of them still remain understudied 5 .…”