Papers by Monica Tallarico Pupo
Quimica Nova, 2008
Endophytes live in association with host plants during all or part of their life cycle without ca... more Endophytes live in association with host plants during all or part of their life cycle without causing any apparent disease. They are considered outstanding and underexploited sources of novel bioactive compounds. Chaetomium globosum was isolated as an endophytic fungus from the healthy leaves of Viguiera robusta. C.globosum is a remarkable producer of chaetoglobosins, which are typically cytotoxic. In this work, chaetoglobosins B (1), D (2) and E (3) have been produced by the endophytic C. globosum strain. Chaetoglobosin B was evaluated against Jurkat (leukemia) and B16F10 (melanoma) tumoral cells and showed 89.55% and 57.10% of inhibition at 0.1 mg mL-1, respectively. Chaetoglobosin B also showed weak antibacterial activity against Staphylococcus aureus (MIC 120 µg/mL) and Escherichia coli (MIC 189 µg/mL).
Analytical and Bioanalytical Chemistry, 2011
The purpose of this study was the development and validation of an LC–MS–MS method for simultaneo... more The purpose of this study was the development and validation of an LC–MS–MS method for simultaneous analysis of ibuprofen (IBP), 2-hydroxyibuprofen (2-OH-IBP) enantiomers, and carboxyibuprofen (COOH-IBP) stereoisomers in fungi culture medium, to investigate the ability of some endophytic fungi to biotransform the chiral drug IBP into its metabolites. Resolution of IBP and the stereoisomers of its main metabolites was achieved by use of a Chiralpak AS-H column (150 × 4.6 mm, 5 μm particle size), column temperature 8 °C, and the mobile phase hexane–isopropanol–trifluoroacetic acid (95: 5: 0.1, v/v) at a flow rate of 1.2 mL min−1. Post-column infusion with 10 mmol L−1 ammonium acetate in methanol at a flow rate of 0.3 mL min−1 was performed to enhance MS detection (positive electrospray ionization). Liquid–liquid extraction was used for sample preparation with hexane–ethyl acetate (1:1, v/v) as extraction solvent. Linearity was obtained in the range 0.1–20 μg mL−1 for IBP, 0.05–7.5 μg mL−1 for each 2-OH-IBP enantiomer, and 0.025–5.0 μg mL−1 for each COOH-IBP stereoisomer (r ≥ 0.99). The coefficients of variation and relative errors obtained in precision and accuracy studies (within-day and between-day) were below 15%. The stability studies showed that the samples were stable (p > 0.05) during freeze and thaw cycles, short-term exposure to room temperature, storage at −20 °C, and biotransformation conditions. Among the six fungi studied, only the strains Nigrospora sphaerica (SS67) and Chaetomium globosum (VR10) biotransformed IBP enantioselectively, with greater formation of the metabolite (+)-(S)-2-OH-IBP. Formation of the COOH-IBP stereoisomers, which involves hydroxylation at C3 and further oxidation to form the carboxyl group, was not observed. Figure Enantioselective biotransformation of ibuprofen to 2-hydroxyibuprofen by endophytic fungi
Electrophoresis, 2009
An experimental design optimization (Box–Behnken design, BBD) was used to develop a CE method for... more An experimental design optimization (Box–Behnken design, BBD) was used to develop a CE method for the simultaneous resolution of propranolol (Prop) and 4-hydroxypropranolol enantiomers and acetaminophen (internal standard). The method was optimized using an uncoated fused silica capillary, carboxymethyl-β-cyclodextrin (CM-β-CD) as chiral selector and triethylamine/phosphoric acid buffer in alkaline conditions. A BBD for four factors was selected to observe the effects of buffer electrolyte concentration, pH, CM-β-CD concentration and voltage on separation responses. Each factor was studied at three levels: high, central and low, and three center points were added. The buffer electrolyte concentration ranged from 25 to 75 mM, the pH ranged from 8 to 9, the CM-β-CD concentration ranged from 3.5 to 4.5% w/v, and the applied run voltage ranged from 14 to 20 kV. The responses evaluated were resolution and migration time for the last peak. The obtained responses were processed by Minitab® to evaluate the significance of the effects and to find the optimum analysis conditions. The best results were obtained using 4% w/v CM-β-CD in 25 mM triethylamine/H3PO4 buffer at pH 9 as running electrolyte and 17 kV of voltage. Resolution values of 1.98 and 1.95 were obtained for Prop and 4-hydroxypropranolol enantiomers, respectively. The total analysis time was around of 15 min. The BBD showed to be an adequate design for the development of a CE method, resulting in a rapid and efficient optimization of the pH and concentration of the buffer, cyclodextrin concentration and applied voltage.
Phytochemistry, 1998
The methanol extract of fruits of Trichilia claussenii yielded the new ?-lactones, (2R,3S, 4S)-3h... more The methanol extract of fruits of Trichilia claussenii yielded the new ?-lactones, (2R,3S, 4S)-3hydroxy-4-methyl-2-(13'-phenyl-1 '-n-tridecyl)-butanolide, (2R, 3 S, 4S)-3 -hydroxy-4-methyl-2-(11 '-phenyl-1 '-nundecyl)-butanolide, (2R,3S, 4S)-3-hydroxy-4-methyl-2-(l'-n-hexadec-7'(Z)-enyl)-butanolide and (2R,3S, 4S)-3-hydroxy-4-methyl-2-(l'-n-tetradecyl)-butanolide. The structures of the isolated compounds were determined on the basis of spectral analysis.
Febs Letters, 2002
The structure of the glycosomal glyceraldehyde-3phosphate dehydrogenase (gGAPDH) from Trypanosoma... more The structure of the glycosomal glyceraldehyde-3phosphate dehydrogenase (gGAPDH) from Trypanosoma cruzi complexed with chalepin, a natural product from Pilocarpus spicatus, has been determined by X-ray crystallography to 1.95 A î resolution. The structure is in the apo form without cofactors in the subunits of the tetrameric gGAPDH in the asymmetric unit. Unequivocal density corresponding to the inhibitor was clearly identified in one monomer. The final refined model of the complex shows extensive conformational changes when compared with the native structure. The mode of binding of chalepin to gGAPDH and its implications for inhibitor design are discussed. ß
Phytochemistry, 1996
The hexane extract of leaves of Trichilia claussenii yielded the new triterpenoid 24-methylene-26... more The hexane extract of leaves of Trichilia claussenii yielded the new triterpenoid 24-methylene-26-hydroxycycloartan-3-one, 24-methylenecycloartanol fatty acids derivatives, caryophyllene epoxide, a mixture of ω-phenyl alkanoic and alkenoic acids, plastocromenol, α-tocopherol, squalene, and a mixture of sitosterol and stigmasterol as free alcohols and esterified by fatty acids. The methanol extract afforded N-methyl-proline, 4-hydroxy-N-methylproline, ω-phenyl alkanoic acids and a mixture of β-O-d-glucopyranosides of
Journal of The Brazilian Chemical Society, 2002
ABSTRACT The methanol extract of stems of Trichilia claussenii yielded three new sesquiterpenoids... more ABSTRACT The methanol extract of stems of Trichilia claussenii yielded three new sesquiterpenoids: 14-hydroxyelemol, germacra-10(14)-en-9,11,15-triol and germacra-3,10(14)-dien-9,11-diol-4-carbaldehyde. Two known sesquiterpenoids beta-eudesmol, cryptomeridiol and the triterpenoid 22,25-dihydroxy-9beta,19-cyclolanost-23-en-3-one were also isolated. The dichloromethane extract from the leaves of T. lepidota afforded a mixture of hydrocarbons (C29H60, C31H64 and C33H68), a mixture of the sesquiterpenes caryophyllene and humulene epoxides, spathulenol, and a series of sterols: 24-methylene-12b-hydroxycholesterol, 24-methyl-12beta-hydroxycholest-4-en-3-one, 24-methylene-12beta-hydroxycholest-5-ene-3-palmitate; a mixture of 24-methylenecholesterol, campesterol, stigmasterol and beta-sitosterol; besides alpha-tocoferol and phytol. From the methanol extract it was isolated N-methyl-4-hydroxyproline. The structures of the isolated compounds were determined on the basis of spectroscopic analysis.
Journal of Computer-aided Molecular Design, 2003
Drug design strategies based on Comparative Molecular Field Analysis (CoMFA) have been used to pr... more Drug design strategies based on Comparative Molecular Field Analysis (CoMFA) have been used to predict the activity of new compounds. The major advantage of this approach is that it permits the analysis of a large number of quantitative descriptors and uses chemometric methods such as partial least squares (PLS) to correlate changes in bioactivity with changes in chemical structure. Because it is often difficult to rationalize all variables affecting the binding affinity of compounds using CoMFA solely, the program GRID was used to describe ligands in terms of their molecular interaction fields, MIFs. The program VolSurf that is able to compress the relevant information present in 3D maps into a few descriptors can treat these GRID fields. The binding affinities of a new set of compounds consisting of 13 coumarins, for one of which the three-dimensional ligand-enzyme bound structure is known, were studied. A final model based on the mentioned programs was independently validated by synthesizing and testing new coumarin derivatives. By relying on our knowledge of the real physical data (i.e., combining crystallographic and binding affinity results), it is also shown that ligand-based design agrees with structure-based design. The compound with the highest binding affinity was the coumarin chalepin, isolated from Rutaceae species, with an IC 50 value of 55.5 µM towards the enzyme glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) from glycosomes of the parasite Trypanosoma cruzi, the causative agent of Chagas' disease. The proposed models from GRID MIFs have revealed the importance of lipophilic interactions in modulating the inhibition, but without excluding the dependence on stereo-electronic properties as found from CoMFA fields.
Phytochemistry, 2000
The fruits of Neoraptua magnifica var. magnifica afforded three new flavonoids: 2'-hydrox... more The fruits of Neoraptua magnifica var. magnifica afforded three new flavonoids: 2'-hydroxy-4,4',-dimethoxy-5',6'-(2'',2''-dimethylpyrano)chalcone, 2'-hydroxy-3,4,4'-trimethoxy-5',6'-(2'',2''-dimethylpyrano)chalcone, and 3',4'-methylenedioxy-5,7-dimethoxyflavone which were identified on the basis of spectroscopic methods. The known flavonoids 2'-hydroxy-3,4,4',5-tetramethoxy-5',6'-(2'',2''-dimethylpyrano)chalcone, 2'-hydroxy-3,4,4',5,6'-pentamethoxychalcone, 3',4'-methylenedioxy-5,6,7-trimethoxyflavone, 3',4'-methylenedioxy-5',5,6,7-tetramethoxyflavone, 3',4',5',5,7-pentamethoxyflavanone and 3',4',5'5,7-pentamethoxyflavone were also identified. The latter flavone was the most active as glyceraldehyde-3-phosphate dehydrogenase-inhibitor.
Bioorganic & Medicinal Chemistry, 2004
This article describes the synthesis and inhibitory activities of a series of new 3-piperonylcoum... more This article describes the synthesis and inhibitory activities of a series of new 3-piperonylcoumarins, designed as inhibitors of glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) from Trypanosoma cruzi. The design was based on the structures of previously identified natural products hits. The most active synthesized derivatives contain heterocyclic rings at position 6. SAR studies, performed by electronic indices methodology (EIM), clustered the molecules in different groups due to the chemical substitutions regarding the biological activity. Molecular modeling studies by docking suggested a different binding mode for the most active derivatives, when compared to natural hit chalepin. Moreover, the coumarin ring seems to act only as a spacer group.
Bioorganic & Medicinal Chemistry, 2007
Twenty hydroxylated and acetoxylated 3-phenylcoumarins were synthesized, and the structure-activi... more Twenty hydroxylated and acetoxylated 3-phenylcoumarins were synthesized, and the structure-activity relationships were investigated by evaluating the ability of these compounds to modulate horseradish peroxidase (HRP) catalytic activity and comparing the results to four flavonoids (quercetin, myricetin, kaempferol and galangin), previously reported as HRP inhibitors. It was observed that 3-phenylcoumarins bearing a catechol group were as active as quercetin and myricetin, which also show this substituent in the B-ring. The presence of 6,2'-dihydroxy group or 6,7,3',4'-tetraacetoxy group in the 3-phenylcoumarin structure also contributed to a significant inhibitory effect on the HRP activity. The catechol-containing 3-phenylcoumarin derivatives also showed free radical scavenger activity. Molecular modeling studies by docking suggested that interactions between the heme group in the HRP active site and the catechol group linked to the flavonoid B-ring or to the 3-phenyl coumarin ring are important to inhibit enzyme catalytic activity.
Phytochemistry, 1997
Meliaceae; pregnane and androstane steroids.
Journal of Molecular Catalysis B-enzymatic
Endophytic microorganisms live inside tissues of host plants apparently do not causing warning to... more Endophytic microorganisms live inside tissues of host plants apparently do not causing warning to them, and are a promising source of bioactive molecules as antimicrobial and antitumoral drugs. In this work, we report the isolation of eugenitin from cultures of the endophyte Mycoleptodiscus indicus and its potential as additive for Aspergillus niveus glucoamylase activation. The glucoamylase hydrolytic activity increased twofold using 5 mM of eugenitin and this activation could be explained by the binding mode of eugenitin with the three-dimensional structure of glucoamylase. The in silico prediction of ligand binding sites revealed at least 9 possible interaction sites able to accommodate eugenitin on glucoamylase from Hypocrea jecorina. Besides, we evaluated the effect of pH and temperature on activity and stability, as well as in the hydrolysis of different substrates and kinetic parameters either in presence or absence of eugenitin. The results displayed by eugenitin as additive to glucoamylase activation are promising and provide novel perspectives for applications of fungal metabolites.
Bioorganic & Medicinal Chemistry Letters, 2004
3D QSAR studies were performed on a library of 120 GAPDH inhibitors, including a series of coumar... more 3D QSAR studies were performed on a library of 120 GAPDH inhibitors, including a series of coumarins, flavonoids, and nucleosides. The VolSurf method was successfully used to calculate surface descriptors for protein-ligand affinity and binding site of the enzyme. PCA/PLS analyses have permitted the evaluation of the structural features crucial for potency, selectivity, and favorable pharmacokinetic properties, and are important for the design of new ligands. Ó 2004 Elsevier Ltd. All rights reserved.
Journal of The Brazilian Chemical Society, 2006
Three known anthraquinones (1,7-dihydroxy-3-methyl-9,10-anthraquinone, 1,6-dihydroxy-3-methyl-9,1... more Three known anthraquinones (1,7-dihydroxy-3-methyl-9,10-anthraquinone, 1,6-dihydroxy-3-methyl-9,10-anthraquinone and 1-hydroxy-3-methyl-9,10-anthraquinone), one new anthraquinone (1,7-dihydroxy-3-hydroxymethyl-9,10-anthraquinone), and two new hexahydroanthraquinone derivatives, dendryols E and F, were isolated from the culture of the endophytic fungus Phoma sorghina, found in association with Tithonia diversifolia (Asteraceae). Their structures were identified on the basis of spectroscopic data, mainly 1D and 2D NMR.
Chromatographia, 2009
A liquid chromatography method is described for the analysis of fluoxetine and norfluoxetine enan... more A liquid chromatography method is described for the analysis of fluoxetine and norfluoxetine enantiomers in fungi cultures. The analytes were separated simultaneously by LC employing a serial system. The resolution was performed using a mobile phase of ethanol: 15 mM ammonium acetate buffer solution, pH 5.9: acetonitrile (77.5:17.5:5, v/v/v). UV detection was at 227 nm. Hexane: isoamyl alcohol (98:2, v/v) was used as extractor solvent. The calibration curves were linear over the concentration range of 12.5–3,750 ng mL−1 (r ≥ 0.996). The values for intra- and inter-day precision and accuracy were ≤10% for all analytes. The validated method was used to evaluate fluoxetine biotransformation to its mammalian metabolite, norfluoxetine, by selected endophytic fungi. Although the desired biotransformation was not observed in the conditions used here, the method could be used to evaluate the biotransformation of fluoxetine by other fungi or to be extended to other matrices with adequate procedures for sample preparation.
Journal of The Brazilian Chemical Society, 2009
A biotransformação da lignana tetraidrofurânica, (-)-grandisina, pelo fungo endofítico Phomopsis ... more A biotransformação da lignana tetraidrofurânica, (-)-grandisina, pelo fungo endofítico Phomopsis sp, obtido de Viguiera arenaria, conduziu à formação de um novo metabólito caracterizado como 3,4-dimetil-2-(4'-hidróxi-3',5'-dimetóxifenil)-5-metóxi-tetraidrofurano. O metabólito foi analisado contra o parasita Trypanosoma cruzi, o agente causador da doença de Chagas, e mostrou uma atividade tripanocida (IC 50 9,8 µmol L -1 ) similar ao precursor natural (IC 50 3,7 µmol L -1 ).
Microbiological Research, 2004
A strain of Penicillium corylophilum isolated from Brazilian soil sample was submitted to differe... more A strain of Penicillium corylophilum isolated from Brazilian soil sample was submitted to different culture conditions to investigate the production of secondary metabolites with antimicrobial activity. The largest number of conidia was obtained after 5 days of incubation in oat medium and the highest level of antimicrobial activity was produced when the fungus culture was developed in the Czapek medium. The activity against Staphylococcus aureus was found only in the chloroform extract from Czapek culture broth, which also showed activity against Micrococcus luteus. Fumiquinozoline F was isolated from the active chloroform extract by using chromatographic methods. The minimal inhibitory concentration (MIC) values for M. luteus and S. aureus were 99 mg/ mL and 137 mg/mL, respectively.
Tetrahedron-asymmetry, 2009
The development of novel biocatalytic methods is a continuously growing area of chemistry, microb... more The development of novel biocatalytic methods is a continuously growing area of chemistry, microbiology, and genetic engineering due to the fact that biocatalysts are selective, easy-to-handle, and environmentally friendly. A wide range of reactions are catalyzed by microorganisms. Fungi can be considered as a promising source of new biocatalysts, mainly for chiral reactions. Chemo-, regio-, and stereoselective processes are very important in the synthesis of many chemical, pharmaceutical, and agrochemical intermediates; active pharmaceuticals; and food ingredients. This report reviews stereoselective reactions mediated by fungi, such as stereoselective hydroxylation, sulfoxidation, epoxidation, Baeyer-Villiger oxidation, deracemization, and stereo-and enantioselective reduction of ketones, published between 2000 and 2007.
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Papers by Monica Tallarico Pupo