Alicia Bardón

Toxic effects of annonaceous acetogenins from Annona cherimolia (Magnoliales: Annonaceae) on Spodoptera frugiperda (Lepidoptera: Noctuidae)

Plants belonging to the family Annonaceae have been commonly described in traditional medicine as remedies against head lice, and for their insecticidal properties. Characteristic constituents from a few genera of these plants are the annonaceous acetogenins. Fourteen annonaceous acetogenins have been isolated from our Argentine collection of the seeds of A. cherimolia. We report herein the antifeedant and insecticidal effects of nine of those acetogenins on Spodoptera frugiperda (J. E. Smith). The acetogenin squamocin, one of the major constituents of the extract, displayed toxic effects on early larval instars when incorporated to the larval diet at a dose of 50xa0μg per g of diet. The remaining annonaceous acetogenins tested, itrabin, asimicin, neoanonin, cherimolin-1, cherimolin-2, almuñequin, motrilin, and tucumanin produced pupal mortality and adult malformations leading to death, when incorporated to the larval diet at the same dose. The evaluation of indices of food consumption, growth, and food utilization indicated that squamocin was the only tested acetogenin to produce significant decrease in the growth rate and to reduce the efficiency with which larvae converted ingested food into biomass. All the acetogenins produced more than 80% pupal mortality with no dependence on the position of the THF rings or the number and location of the OH groups.

Antifeedant and toxic effects of acetogenins from Annona montana on Spodoptera frugiperda

Several species of the large family of tropical plants Annonaceae have been intensely investigated over the last 20xa0years, mainly because of the discovery of annonaceous acetogenins. These compounds are powerful cytotoxics, with potential applications as insecticides, antiparasitics, acaricides, fungicides, and antitumor drugs. Annona montana Macfad. (Annonaceae) grows in Santa Cruz de la Sierra, Bolivia, where an infusion of leaves is used for the treatment of lice, influenza, and insomnia. The major acetogenins from a Bolivian collection of A. montana, annonacin (1), cis-annonacin-10-one (2), densicomacin-1 (3), gigantetronenin (4), murihexocin-B (5), and tucupentol (6), were evaluated for their antifeedant and toxic effects on Spodoptera frugiperda Smith (Lepidoptera: Noctuidae), a serious pest affecting corn crops in Argentina. All the acetogenins produced 100% mortality during the larval or pupal stages at 100xa0μg of treatment per gram of diet. In addition, compounds 2, 3, and 4 deterred more than 80% feeding at the same dose. Relative toxicity values of LD50 for the strongest larvicidal compounds 1, 2, and 4 were determined, indicating that the three compounds are effective natural insecticides. This is the first report on the antifeedant and toxic effects produced by the particular type of acetogenins, the mono-THF acetogenins, on the lepidopteran S. frugiperda. No correlation was detected between the toxicity of the mentioned compounds to larvae and the known capacity of the acetogenins 1, 2, and 4 to inhibit the NADH oxidase, indicating that the inhibition of the mitochondrial complex I is not the only cause for larval mortality of S. frugiperda.

Inhibition of quorum sensing in Pseudomonas aeruginosa by sesquiterpene lactones.

Six sesquiterpene lactones (SLs) of the goyazensolide and isogoyazensolide-type isolated from the Argentine herb Centratherum punctatum were evaluated on their ability to inhibit virulence factors of Pseudomonas aeruginosa ATCC 27853. Although compounds were not able to completely inhibit bacterial growth at 200μg/ml, the SLs do altered biofilm formation, elastase activity, and production of N-acyl-homoserinelactones (AHLs) which are known quorum sensing autoinducers at lower concentration. Compounds 2, 3, and 5 displayed significant inhibitory effects on P. aeruginosa biofilm formation at 0.5μg/ml being compound 3 (1.32μM) the most potent (42%). Compounds 2, 3, 4, 5 and 6, inhibited 39, 44, 42, 32 and 35% the production of AHLs at 100μg/ml and inhibited by more than 50% the elastase activity at 0.5μg/ml. Our results clearly indicated that sesquiterpene lactones are good candidates for the development of new antimicrobial agents acting not as bactericidal but as antipathogenic agents.

Sesqui- and triterpenoids from the liverwort Lepidozia chordulifera inhibitors of bacterial biofilm and elastase activity of human pathogenic bacteria

Five dammarane-type triterpenoids, five pentacyclic triterpenoids (three of them carrying a carboxylic acid group), and two aromadendrane-type sesquiterpenoids were isolated from an Argentinian collection of the liverwort Lepidozia chordulifera. Compounds were characterized by comparison of their spectral data with those previously reported and tested in their ability to control bacterial growth, biofilm formation, bacterial Quorum Sensing process (QS), and elastase activity of Pseudomonas aeruginosa, as well as bacterial growth and biofilm formation of Staphylococcus aureus. The key role played by biofilm and elastase activity in bacterial virulence make them a potential target for the development of antibacterial agents. The aromadendrane-type sesquiterpenoid viridiflorol was the most potent biofilm formation inhibitor, producing 60% inhibition in P. aeruginosa and 40% in S. aureus at 50µg/ml. Ursolic and betulinic acids (two of the pentacyclic triterpenoids isolated) were able to reduce 96 and 92% the elastase activity of P. aeruginosa at 50µg/ml, respectively. Among the analyzed triterpenoids, those that carry a dammarane skeleton were the most potent inhibitors of the P. aeruginosa biofilm formation and were active against both P. aeruginosa and S. aureus. Subsequently, a computer-assisted study of the triterpenoid compounds was carried out for a better understanding of the structure-activity relationships.

In vivo and in vitro antibacterial activity of acanthospermal B, a sesquiterpene lactone isolated from Acanthospermum hispidum

Acanthospermal B (AcB), the major sesquiterpene lactone (SL) of Acanthospermum hispidum, an herb widely spread in Argentina, is a selective antibacterial agent against Enterococcus faecalis and Staphylococcus aureus, but inactive on Gram‐negative and Lactobacillus. Methicillin‐resistant Staphylococcus aureus (MRSA) is one of the main microorganisms involved in human chronic infection. A balbc mouse skin infection model was developed to reproduce the lesions caused by acute and chronic infections produced by MRSA. After determination of the maximum concentration of AcB unable to produce tissular injury after intradermal injection, the anti‐MRSA effect of AcB was evaluated on skin, liver and spleen tissues of infected mice. AcB, at doses of 2.5u2009mg/kg, produced a ten times decrease of MRSA growth in skin infection. In addition, the same dose prevented the dissemination to liver and/or spleen. AcB also displayed a bacteriostatic effect, in vitro, on MRSA cultures at 50u2009µg/mL that seems to be caused by partial denaturation of total bacterial DNA and/or inhibition of the PCR reaction in not denaturized DNA. Finally, total MRSA cell wall lysis occurred at a concentration of 100u2009µg/mL of AcB after 2u2009h of exposure. Copyright

Active sesquiterpene lactones against Leishmania amazonensis and Leishmania braziliensis.

Abstract Seventeen sesquiterpene lactones (SLs) isolated from five species of the tribe Vernonieae were evaluated for their in vitro activity against promastigotes of Leishmania amazonensis and Leishmania braziliensis. Additionally, a quantitative structure activity relationship has been made, since all these natural compounds were found to have potent to mild antileishmanial properties. The most active compounds against L. braziliensis were 16 and 17 (IC50 values 1.45 and 1.34 μM, respectively), followed by compound 15 with IC50 value of 1.60 μM against L. amazonensis. The three glaucolide-type SLs (4−6) were the least active against both parasites. The computational study allowed us to establish that lipophilicity and polarisability play an important role in the antiparasitic activity. This is the first report of the known germacradiendiolides 16 and 17 from Elephantopus mollis. The activity data of the compounds 1−17 assayed against Leishmania parasites are reported here for the first time.

Penicillium commune metabolic profile as a promising source of antipathogenic natural products.

Penicillium is an important genus of ascomycetous fungi in the environment and in food and drug production. This paper aims to investigate statins and antipathogenic natural products from a Penicillium commune environmental isolate. Fractions (F1, F2, F3 and F4) were obtained from an ethyl acetate extract. Direct insertion probe/electron ionisation/ion trap detection mass spectrometry (MS and MS/MS) identified lovastatin (1) in F1, while GC-MS showed that 3-isobutylhexahydropyrrolo[1,2-a]pyrazine-1,4-dione (2) was the main constituent of F2 (49.34%). F4 presented 3 (16.38%) as an analogue of 2 and their known structures were similar to that of an autoinducer-signal. F1 produced a significant decrease in the Pseudomonas aeruginosa biofilms, which is the main cause of bacterial pathogenicity. F2 and F4 were effective against Staphylococcus aureus biofilms, but when F2 was associated with oxacillin, it showed an important activity against both bacteria. These novel results suggest that P. commune INTA1 is a new source of promising antipathogenic products.

Insecticidal constituents from the argentine liverwort Plagiochila bursata.

The new 2,3‐secoaromadendrane 1, together with the known compounds plagiochilines A and M (2 and 3, resp.), fusicogigantone A (4), and 1,4‐dimethylazulene (5) were isolated from an Argentine collection of the liverwort Plagiochila bursata. Structures were elucidated by extensive 1D‐ and 2D‐NMR studies. Compounds 2 and 4, incorporated to the larval diet at 100u2005μg per g of diet, reduced the larval growth of Spodoptera frugiperda (Lepidoptera: Noctuidae) by 66±29% and 25±8% and produced 55 and 75% larval mortality at early instars and 20 and 25% pupal mortality, respectively. Treatment with compound 2 also produced abdomen and wing malformation in adults leading to impossibility to mate.

Activity of a novel compound produced by Aspergillus parasiticus in the presence of red flour beetle Tribolium castaneum against Pseudomonas aeruginosa and coleopteran insects

AbstractAspergillus is a promising source of bioactive secondary metabolites. The addition of insect-derived material in the broth culture could trigger the biosynthesis of insecticidal and antimicrobial compounds by entomopathogenic fungus (EF). Insects inhabit diverse niches and interact with various bacteria, for this reason, when a fungus kills an insect should inhibit the insect’s gut bacteria to prevent the insect consumption by bacteria. According with this hypothesis, the EF is able to produce substances that inhibit bacteria growth or bacteria virulence strategies. In the present, investigation is demonstrated that the addition of Tribolium castaneum Herbst (Coleoptera: Tenebrionidae) components (2xa0% w/v) in a culture of saprophytic fungus Aspergillus parasiticus MOR 3 induces the production of a novel compound present inside mycelium 2-(4-bromophenyl)-2-oxoethyl benzoate, that is reported here for the first time as a natural product of A. parasiticus. In addition, increased significantly the fungal extracellular production of undecyl 4-fluorobenzoate. The mycelium extract (ME) at 250xa0μg per g of diet on adult population of T. castaneum produced an alteration of the feeding behavior of coleopteran insects (Repellency indexxa0=xa0+30). The fraction derived from ME (Fr2) that contained the organobromine compound, 2-(4-bromophenyl)-2-oxoethyl benzoate had the highest inhibition of the Pseudomonas aeruginosa virulence factors like elastase enzyme (49xa0%) at 5xa0μg/ml and biofilm formation (43xa0%) at 100xa0μg/ml. The results suggest that the extract from mycelium of a non-aflatoxigenic A. parasiticus MOR 3 strain is a potential candidate as food coleopteran repellent as well as an anti-virulence strategy of P. aeruginosa.n

Unusual terpenylated acylphloroglucinols from Dryopteris wallichiana.

Four unusual terpenylated acylphloroglucinols were isolated from the diethyl ether extract of the scales and rhizomes of the fern Dryopteris wallichiana together with the known compounds albaspidins AA and AB, and filixic acids ABA and ABB. Structures of the isolated compounds were established by extensive spectroscopic analysis and their absolute configuration at C-14″ was determined by comparing their CD spectra with those simulated for the respective isomers. Pure acylphloroglucinols displayed moderate in vitro nematocidal activity against L4 stage larvae of Nippostrongylus brasiliensis (LD₅₀=22-121 μM).