Andrimid production at low temperature by a psychrotolerant Serratia proteamaculans strain.

Andrimid, a known non-ribosomal pseudo-peptide antibiotic, was isolated from a psychrotolerant Serratia proteamaculans strain. The antibiotic peptide was produced at low temperature (8 °C) in a 7.5 l BIOFLO 101 bioreactor under batch culture mode. Andrimid activity from S. proteamaculans culture was only detected at 25 °C and below and potent antibacterial activity was revealed against both, pathogenic and non-pathogenic bacteria. Minimal inhibitory concentration values determined by microdilution experiments varied in the range between 0.01 and 0.78 µg/ml. Antimicrobial purification and structure elucidation were carried out by LC-MS/MS and ¹H/¹³C NMR approaches. The effects on the ultrastructure of sensitive Escherichia coli 35,218 cells were observed by transmission electron microscopy at different inhibition stages. This work demonstrated the significance of bioprospection from cold environments through the screening of microorganisms with ability to produce cold-active biomolecules of biotechnological interest. S. proteamaculans 136 was revealed as a novel microbial source for andrimid production at low temperatures, showing biotechnological potential to be applied in cryopreservation, food or cosmetic industries against pathogenic bacteria.

Discovery of ß-glucosidase inhibitors from a chemically engineered extract prepared through ethanolysis.

A series of vegetal extracts have been chemically altered by ethanolysis. The effect of the reaction on the inhibition of the enzyme ß-glucosidase properties of the mixtures was studied using thin layer chromatography (TLC) with biodetection. Glucosidase inhibitory activity guided fractionation of one of the produced chemically engineered extracts led to the isolation of apigenin and ethyl p-cumarate. Both compounds were generated during the chemical modification step.

Two New Furanoeremophilanes from Senecio santelisis.

From an Argentine collection of Senecio santelisis Phil., the new furanoeremophilanoids, (10betaH)-6beta-acetoxy-1alpha-hydroxyfuranoeremophilan-9-one (1) and (10betaH)-1alpha-hydroxy-6beta-(propanoyloxy)furanoeremophilan-9-one (2), together with the known (10alphaH)-6beta-acetoxy-1alpha-hydroxyfuranoeremophilan-9-one (3), (10alphaH)-1alpha,6beta-diacetoxyfuranoeremophilan-9-one (4), and (10alphaH)-1alpha-hydroxy-6beta-(propanoyloxy)furanoeremophilan-9-one (5) were isolated. Their structures and relative configurations were established on the basis of spectroscopic analysis. CHCl3 Extract and pure compounds were evaluated for their antifungal activity. Compound 5 exhibited remarkable mycelial growth inhibition against B. cinerea with an IC(50) value of 21.4 microg/ml.

Chemically engineered extracts: bioactivity alteration through sulfonylation.

The chemical composition and the biomolecular properties of a series of crude plant extracts were altered without previous knowledge of their detailed chemical composition.

Molluscicidal sesquiterpene lactones from species of the tribe Vernonieae (Compositae).

Schistosomiasis is caused by parasitic flatworms of the genus Schistosoma, and some snails, particularly of the genus Biomphalaria (Planorbidae), are directly implicated in the transmission of the disease. Continuing with our investigations of bioactive plant constituents, we evaluated and report in the present article, the molluscicidal effects of 16 sesquiterpene lactones, as well as the commercial reagents tetrahydrofuran, furfural, and furfuryl alcohol, on an adult population of B. peregrina. The natural sesquiterpene lactones tested are characteristic constituents of species of the tribe Vernonieae, family Asteraceae. Compounds 1-3 and 7 came from a Bolivian collection of Vernonanthura pinguis, compounds 4 and 5 from an Argentine collection of Cyrtocymura cincta var. cincta, 6 was obtained from a Bolivian collection of Eirmocephala megaphylla, 8-14 from an Argentine collection of Centratherum punctatum ssp. punctatum, and compounds 15 and 16 were obtained by chemical derivatization from 5 and 14, respectively. Ten of the sesquiterpene lactones displayed moderate molluscicidal activity (LD50<100 microg/ml). Commercial reagents were inactive.

Eudesmanes from Pluchea sagittalis. Their antifeedant activity on Spodoptera frugiperda.

Eudesmane-type sesquiterpenoids 3alpha-(2,3-epoxy-2-methylbutyryloxy)-4alpha-formoxy-11-hydroxy-6,7-dehydroeudesman-8-one (1) and 3alpha-(2,3-epoxy-2-methylbutyryloxy)-4alpha,7alpha,11-trihydroxyeudesman-8-one (2), together with 10 known structurally related eudesmanes were isolated from the CHCl3 extract of aerial parts of Pluchea sagittalis (Lamarck) Cabrera. Their structures were deduced by extensive application of 1 and 2D NMR spectroscopic techniques and high and low resolution CIMS. X-ray crystallographic analysis of the known compound 3alpha-(2,3-epoxy-2-methylbutyryloxy)-4alpha-formoxycuauthemone (9) is reported here for the first time, and confirms the structural features for the series of the reported eudesmanes. All eudesmanes were tested for their antifeedant activity by incorporating them to an artificial diet of larvae of the polyphagous insect Spodoptera frugiperda at a concentration of 100ppm. Our results, from feeding choice tests, indicated that most of the compounds deter larval feeding at the cited concentration.

Chemically engineered extracts as an alternative source of bioactive natural product-like compounds.

The access to libraries of molecules with interesting biomolecular properties is a limiting step in the drug discovery process. By virtue of a long molecular evolution process, natural products are recognized as biologically validated starting points in structural space for library development. We introduce here a strategy to generate natural product-like libraries. A semisynthetic mixture of compounds was produced by diversification of a natural product extract through the chemical transformation of common chemical functionalities in natural products into chemical functionalities rarely found in nature. The resulting mixture showed antifungal activity against Candida albicans, whereas the starting extract did not show such activity. Bioguided fractionation led to the isolation of a previously undescribed active semisynthetic pyrazole. The result illustrates how biological activity can be generated by designed chemical diversification of a natural product mixture, and represents the proof of principle of an alternative strategy for producing natural product-like libraries from natural products libraries.

Synthesis, structure and catalase-like activity of dimanganese(III) complexes of 1,5-bis(X-salicylidenamino)pentan-3-ol (X = 3- and 5-methyl). Influence of phenyl-ring substituents on catalytic activity.

The diMn(III) complexes [Mn2(5-Me-salpentO)(mu-MeO)(mu-AcO)(H2O)Br] (1) and [Mn2(3-Me-salpentO)(mu-MeO)(mu-AcO)(MeOH)2]Br (2), where salpentOH = 1,5-bis(salicylidenamino)pentan-3-ol, were synthesised and structurally characterized. The two complexes include a bis(micro-alkoxo)(micro-acetato) triply-bridged diMn(III) core with an Mn...Mn separation of 2.93-2.94 A, the structure of which is retained upon dissolution. Complexes 1 and 2 show catalytic activity toward disproportionation of H2O2, with first-order dependence on the catalyst, and saturation kinetics on [H2O2], in methanol and DMF. In DMF, the two complexes are able to disproportionate at least 1500 eq. of H2O2 without significant decomposition, while in methanol, they rapidly lose activity with formation of a non-coupled Mn(II) species. Electrospray ionisation mass spectrometry, EPR and UV/vis spectroscopy used to monitor the reaction suggest that the major active form of the catalyst occurs in the Mn2(III) oxidation state during cycling. The correlation between log(k(cat)) and the redox potentials of 1, 2 and analogous complexes of other X-salpentOH derivatives indicates that, in this series, the oxidation of the catalyst is probably the rate-limiting step in the catalytic cycle. It is also noted that formation of the catalyst-peroxide adduct is more sensitive to steric effects in DMF than in methanol. Overall, kinetics and spectroscopic studies of H2O2 dismutation by these complexes converge at a catalytic cycle that involves the Mn2(III) and Mn2(IV) oxidation states.

An unusual homoisoflavanone and a structurally-related dihydrochalcone from Polygonum ferrugineum (Polygonaceae).

The homoisoflavanone 5,7-dihydroxy-6-methoxy-3-(9-hydroxy-phenylmethyl)-chroman-4-one (1) and its structurally related 2',4',6'-trihydroxy-3'-methoxy-alpha-hydroxymethyl-beta-hydroxy-dihydrochalcone (2) along with the known pashanone (3), flavokawin B (4) and cardamonin or alpinetin chalcone (5) pinostrobin (6) and 5,8-dimethoxy-7-hydroxychroman-4-one (7) were isolated from dry leaves of Polygonum ferrugineum (Polygonaceae). To our knowledge, this is the first report of the isolation of a homoisoflavanone from the Polygonum genus and the Polygonaceae family, and could be an important chemotaxonomic finding. In addition, the pattern of substitution of this homoisoflavanone is different from others previously reported.