Among HIV-1 reverse transcriptase (RT)-associated functions, DNA polymerase and Ribonuclease H (RNase H) are both essential for HIV replication and excellent targets for drug development. While all RT inhibitors approved for therapy target the DNA polymerase activity, there is the pressing need for new RT inhibitors possibly targeting the RNase H function. In the last 20 years, many natural substances have shown antiviral activity against HIV-1, but only a few against the RNase H function. In this study, we have tested the ethanolic extracts obtained by the Hypericum hircinum L. (Hypericaceae) growing in Sardinia (Italy) on the HIV-1 RT-associated RNase H function and found that they have inhibitory effects. Active extracts were fractionated up to obtain the main components that have been isolated, tested, and identified to be betulinic acid, shikimic acid, chlorogenic acid, quercetin, 5,7,3',5'-tetrahydroxyflavanone, and 5,7,3',5'-tetrahydroxyflavanone 7-O-glucoside. Betulinic acid and 5,7,3',5'-tetrahydroxyflavanone 7-O-glucoside were active on both RT-associated activities, and betulinic acid was also active on HIV-1 mutant RTs resistant to efavirenz. Overall, our results suggest that some of these compounds inhibit the HIV-1 RT binding to an allosteric site previously described for other natural compounds and are potential leads for further drug development of a single molecules having dual inhibitory activity.

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A complete chemical investigation of Achillea ligustica All. growing at Lipari (Aeolian Island, Sicily) has been carried out. Seventeen metabolites have been isolated and characterised from dichloromethane and methanol extracts of flowers and aerial parts, and GC/MS analyses of petroleum ether extracts was carried out, revealing a composition in sesquiterpenoids similar to those reported for populations from Greece, Sicily and Algeria, showing the presence of (3RS,6RS)-2,6-dimethyl-1,7-octadiene-3,6-diol (1), 2,6-dimethyl-octa-3(E),7-diene-2,6-diol (2), iso-seco-tanapartholide (3) from DCM fraction. In addition from the methanolic extract of the aerial parts, peculiar flavonoid glucuronides have been isolated: i.e. apigenin-7-O-glucuronide (12) and quercetin 3-O-glucuronide (14). These metabolites have been reported in this species for the first time. The isolated flavonoids were previously recognised in several species of this complex genus and for this reason seems to be highly retained secondary metabolites of importance from the chemotaxonomic point of view.

The IRMPD spectrum of the G-quartet-Na(+) complex, in combination with an ab initio molecular dynamic simulation, revealed the presence of two metastable populations of conformers separated by a free energy barrier easily accessible at room temperature.

A combined computational and infrared multiphoton dissociation (IRMPD) spectroscopic investigation shows that protonated d-(+)-biotin, formed in the gas phase by ESI-MS, acquires a folded structure with proton bonding between the ureido and valeryl carbonyls, and that only a single conformer of such a structure predominates. A uniform frequency vs distance correlation function is proposed for the O(+)-H···O and N-H···O bonds involved in the folded conformers of O2'-protonated d-(+)-biotin in the gas phase which, therefore, depends exclusively on the corresponding geometric parameters.