Diego A. Cifuente

Clerodane diterpenes from Baccharis sagittalis: insect antifeedant activity.

Two clerodane-type diterpene glycosides esters, which were studied as peracetyl derivatives, together with the known diterpene marrubiagenine, were isolated from the aerial part of Baccharis sagittalis (Less). Their structures were established by spectroscopic methods. Antifeedant activity toward Tenebrio molitor larvae of the isolated compounds along with six other diterpenes was evaluated and some structure-antifeedant bioactivity relationships are reported.

Atypical regioselective biohydrolysis on steroidal oxiranes by Aspergillus niger whole cells : Some stereochemical features

5,6-Epoxycholestan-3beta-ol derivatives were hydrolyzed in a diastereoconvergent manner by growing and resting cells of several strains of Aspergillus niger, particularly A. niger ATCC 11394. These strains displayed opposite regioselectivity toward each isomer in an alpha and beta epoxide mixture, thus, the nucleophilic attack took place at the less substituted and the most substituted carbon atom on each diasteromer, respectively. These biocatalysts opened trisubstituted oxiranes but were unable to hydrolyze the disubstituted oxiranes in the tested sterol derivatives. These findings suggest that A. niger strains possess another hydrolytic ability different from the commercial A. niger epoxide hydrolase (EH) that did not accept this kind of steroidal oxiranes as substrates.

An abietane diterpene from Salvia cuspidata and some new derivatives are active against Trypanosoma cruzi.

The Plant Kingdom is an excellent source for obtaining natural compounds with antiprotozoal activity. In the present work, we studied the effect of the diterpene 12-hydroxy-11,14-diketo-6,8,12-abietatrien-19,20-olide (HABTO) obtained from the aerial parts of Salvia cuspidata on Trypanosoma cruzi epimastigotes. This compound was found to inhibit parasite growth even at low concentrations (IC50 5 μg/mL) and with low toxicity on mammalian cells. In addition, this diterpene induced an intense vacuolization within the parasites. In order to obtain analogs with greater lipophilicity, chemical modifications on the enol moiety were carried out to obtain the acetyl (AABTO), the sylil (SABTO) and the allyl (ALLABTO) derivatives. We observed that the SABTO was the most effective one on the parasites, and the effect could be attributed to a greater lipophilicity of this compound. Taking into account these data we conclude that the increase of lipophilicity by chemical modifications is an adequate strategy for improving the trypanocidal activity of this kind abietane diterpenes.

Stereo- and regioselective hydroxylation of grindelic acid derivatives by Aspergillus niger

Stereo- and regioselective hydroxylation of grindelane derivatives on position 3β was catalyzed by cultures of Aspergillus niger. Grindelic acid (1), methyl grindelate (2), 15-hydroxy-7(8)-en-9α,13(S)-oxide-ent-labdane (3) and 7α,8α-epoxymethylgrindelate (4) were bioconverted into the corresponding 3β-hydroxy derivatives as the only biotransformation products. 13(S),15-dihydroxy-8(9)-en-ent-labdane (5) remained unreacted under the same conditions. The conformational and electronic studies of the substrates are discussed.

Two new labdane diterpene glycosides from flowers of Baccharis medullosa DC.

Abstract From the flowers of Baccharis medullosa DC (Asteraceae) two new ent-labdane-type diterpene glycosides were isolated. Structures were established by application of various spectroscopic techniques. The sugar residues were identified after acid hydrolysis of the isolated products.

Mass spectrometry studies of lycodine‐type Lycopodium alkaloids: sauroxine and N‐demethylsauroxine

RATIONALE Sauroxine and N-demethylsauroxine are lycodine-type Lycopodium alkaloids. In recent years, Lycopodium alkaloids have gained significant interest due to their unique skeletal characteristics as well as due to their acetylcholinesterase activity. It is known that drugs that inhibit acetylcholinesterase can be used to treat the early stages of Alzheimers disease. METHODS Sauroxine and N-demethylsauroxine were isolated from the aerial parts of Huperzia saururus (Lam.) Trevis. Electron ionization mass spectrometry (EI-MS) (low resolution) and collision-induced dissociation tandem mass spectrometry (CID-MS/MS) fragmentation was conducted using an ion trap, GCQ Plus mass spectrometer with MS/MS. Electron ionization high-resolution mass spectrometry (EI-HRMS) was performed in a magnetic sector mass spectrometer (Micromass VG). RESULTS Using GC/EI-CID-MS/MS we obtained different fragmentation routes that connect all the ionic populations. In addition, the use of EI-HRMS allowed us to measure the exact masses of all the fragment ions, and, with all this information gathered, we tried to establish a fragmentation scheme concordant with the ascendant and descendant species. CONCLUSIONS The mass spectrometry studies presented in this work complete our mass studies of Lycopodium alkaloids. The mass spectrometry work presented has been very useful to confirm the structures as well as to support the biogenetic relationships between the lycodine-type Lycopodium alkaloids: sauroxine and N-demethylsauroxine.

A new semisynthetic derivative of sauroine induces LTP in hippocampal slices and improves learning performance in the Morris Water Maze.

Two semisynthetic acetyl derivatives of the alkaloid sauroine from Huperzia saururus, monoacetyl sauroine, and diacetyl sauroine (DAS) were obtained and their chemical structures were analyzed by NMR. While monoacetyl sauroine is the typical product of acetylation, DAS is an unexpected derivative related to the keto‐enol formation of sauroine. Recordings of field excitatory post‐synaptic potentials from the CA1 region of rat hippocampal slices showed that only DAS acutely applied induced chemical long‐term potentiation (LTP) in a dose‐dependent manner with an EC50 of 1.15 ± 0.09 μM. This effect was blocked by 10 μM D(‐)‐2‐amino‐5‐phosphonopentanoic acid (AP5), suggesting dependence on the NMDA receptor. DAS significantly increased NMDA receptor‐dependent excitatory post‐synaptic currents without affecting α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate receptor‐dependent currents. Repetitive administration of DAS improved visuo‐spatial learning in the Morris Water Maze. In slices from rats tested in the Morris Water Maze, LTP resulting from electrical synaptic stimulation was 2.5 times larger than in controls. Concentration of DAS measured in the brain after repetitive administration was 29.5 μM. We conclude that slices perfused with DAS display a robust NMDA receptor‐dependent chemical LTP. During chronic treatment, DAS enhances learning abilities through a metaplastic mechanism as revealed by the augmentation of LTP in slices. DAS, therefore, may be a promising compound as a nootropic therapeutic drug.

Anti-inflammatory Activity and Antioxidant Potential of Aqueous Extracts from Stem Bark of Geoffroea decorticans

In the present work we investigated, for the first time, the anti-inflammatory activity and the antioxidant properties of aqueous and ethanolic extracts, obtained from stem bark of Geoffroea decorticans (Gill. ex Hook. et Arn.) Burk. (Fabaceae). G. decorticans, commonly known as “chañar” or “chañarcillo”, is a traditional argentinean plant used as emollient, balsamic, antitussive, expectorant and anti-inflammatory. The stem bark was collected from San Francisco del Monte de Oro, San Luis, Argentina. Anti-inflammatory activity was evaluated by carrageenan-induced paw edema in rats. Antioxidant activity was tested using 1,1-Diphenyl-2-picrylhydrazyl radical-scavenging activity (DPPH), 2,2 ́-Azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) radical scavenging activity (ABTS) and ferric ion-reducing power (RP-Fe) assays. Aqueous extract 10% p/v showed anti-inflammatory activity (3h, 48% inhibition, 5h 37% inhibition and 7h 17% inhibition) and antioxidant activity (DPPH, IC50 (mg/mL) = 0.098 ± 0.032; ABTS, IC50 (mg/mL) = 0.022 ± 0.343, RP-Fe IC50 (mg/mL) = 1.124 ± 0.146). In the other hand, the ethanolic extract 5% p/v, presented anti-inflammatory activity (3h, 34% inhibition, 5h 38% inhibition and 7h 35% inhibition) and antioxidant activity (DPPH, IC50 (mg/mL) = 0.133 ± 0.027; ABTS, IC50 (mg/mL) = 0.086 ± 0.262, RP-Fe IC50 (mg/mL) = 7.089 ± 0.104). These results suggest that, also fruits, the aqueous and ethanolic extracts from the stem bark of G. decorticans present significant anti-inflammatory activity and antioxidant properties.