El Correo gallego : diario político de la mañana: Ano LVIII Número 20110 - 1936 xullo 26

<p>Reverse transcriptase (RT)-associated DNA polymerase (RDDP) and ribonucleaser H (RNase H) functions are both essential for HIV-1 genome replication, and the identification of new inhibitors to block both of them is a goal actively pursued by the scientific community. In this field, natural extracts have shown a great potential as source of new antivirals. In the present work, we investigated the effect of <i>Uvaria angolensis</i> extracts on the HIV-1 reverse transcriptase-associated DNA polymerase and ribonuclease H activities. The <i>U. angolensis</i> stem bark methanol extract inhibit both HIV-1 RNase H function and RDDP activity with IC₅₀ values of 1.0 ± 0.2 and 0.62 ± 0.15 μg/mL, respectively and, after been fractionated with different solvents, its solid residue showed an IC₅₀ of 0.10 ± 0.03 and of 0.23 ± 0.04 μg/mL against RNase H and RDDP, respectively, hence laying the bases for further studies for identification of single active components.</p

¹H NMR spectra of MeOH/H₂O extract of <i>H</i>. <i>scruglii</i>.

<p>Numbers indicate the diagnostic signals of the isolated secondary metabolites 1–6.</p

Chemical structures of known metabolites isolated from <i>H</i>. <i>scruglii</i>.

<p>Chemical structures of known metabolites isolated from <i>H</i>. <i>scruglii</i>.</p

Time-of-addition assay.

<p>The target of the antiviral compound <b>3</b> (Cp3) was identified by comparing its activity in the time scale to those of reference drugs: Maraviroc (MCV, entry inhibitor), Lamivudine (LAM, RT inhibitor), Dolutegravir (DTG, IN inhibitor). Cp3 was ineffective once the virus retrotranscribed its genome.</p

Antiviral activity of compounds 1, 2 and 3 on HIV AD8 laboratory strain in TZM-bl cells.

<p>Cells were infected with 300 TCID50/mL and treated with compounds isolated from <i>H</i>. <i>scruglii</i> at seven different concentration. EC₅₀ values ranged from 3.5 to 8 <b>μ</b>M. Only active compounds were shown.</p

Prenylated phloroglucinols from <i>Hypericum scruglii</i>, an endemic species of Sardinia (Italy), as new dual HIV-1 inhibitors effective on HIV-1 replication - Fig 3

<p>A: Chemical structure of the novel phloroglucinol 3 from <i>H</i>. <i>scruglii</i>; B: diagnostic 2D NMR correlations.</p

Effects of compounds isolated from <i>Hypericum scruglii</i> on the HIV-1 replication.

<p>Effects of compounds isolated from <i>Hypericum scruglii</i> on the HIV-1 replication.</p

1D and 2D NMR data of compound 3 in CD₃OD.

<p>1D and 2D NMR data of compound 3 in CD₃OD.</p

Effects of compounds isolated from <i>Hypericum scruglii</i> on the HIV-1 RT-associated activities and IN activities in presence of LEDGF/p75.

<p>Effects of compounds isolated from <i>Hypericum scruglii</i> on the HIV-1 RT-associated activities and IN activities in presence of LEDGF/p75.</p

<i>N</i>‑Acylbenzenesulfonamide Dihydro-1,3,4-oxadiazole Hybrids: Seeking Selectivity toward Carbonic Anhydrase Isoforms

A series of <i>N</i>-acylbenzenesulfonamide dihydro-1,3,4-oxadiazole hybrids (<b>EMAC8000a–m</b>) was designed and synthesized with the aim to target tumor associated carbonic anhydrase (hCA) isoforms IX and XII. Most of the compounds were selective inhibitors of the tumor associated hCA XII. Moreover, resolution of <b>EMAC8000d</b> racemic mixture led to the isolation of the levorotatory eutomer exhibiting an increase of hCA XII inhibition potency and selectivity with respect to hCA II. Computational studies corroborated these data. Overall our data indicate that both substitution pattern and stereochemistry of dihydro-1,3,4-oxadiazole could be considered as key factors to determine activity and selectivity toward hCA isozymes. These results can provide further indication for the design and optimization of selective hCA inhibitors