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1.
Mem Inst Oswaldo Cruz ; 115: e190396, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32321154

RESUMO

BACKGROUND: Nanoparticles (NPs) are viable candidates as carriers of exogenous materials into cells via transfection and can be used in the DNA vaccination strategy against leptospirosis. OBJECTIVES: We evaluated the efficiency of halloysite clay nanotubes (HNTs) and amine-functionalised multi-walled carbon nanotubes (NH2-MWCNTs) in facilitating recombinant LemA antigen (rLemA) expression and protecting Golden Syrian hamsters (Mesocricetus auratus) against Leptospira interrogans lethal infection. METHODS: An indirect immunofluorescent technique was used to investigate the potency of HNTs and NH2-MWCNTs in enhancing the transfection and expression efficiency of the DNA vaccine in Chinese hamster ovary (CHO) cells. Hamsters were immunised with two doses of vaccines HNT-pTARGET/lemA, NH2-MWCNTs-pTARGET/lemA, pTARGET/lemA, and empty pTARGET (control), and the efficacy was determined in terms of humoral immune response and protection against a lethal challenge. FINDINGS: rLemA DNA vaccines carried by NPs were able to transfect CHO cells effectively, inducing IgG immune response in hamsters (p < 0.05), and did not exhibit cytotoxic effects. Furthermore, 83.3% of the hamsters immunised with NH2-MWCNTs-pTARGET/lemA were protected against the lethal challenge (p < 0.01), and 66.7% of hamsters immunised with HNT-pTARGET/lemA survived (p < 0.05). MAIN CONCLUSIONS: NH2-MWCNTs and HNTs can act as antigen carriers for mammalian cells and are suitable for DNA nanovaccine delivery.


Assuntos
Antígenos de Bactérias/administração & dosagem , Proteínas de Bactérias/administração & dosagem , Vacinas Bacterianas/administração & dosagem , Leptospirose/prevenção & controle , Fatores de Transcrição/administração & dosagem , Vacinas de DNA/administração & dosagem , Animais , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Vacinas Bacterianas/imunologia , Cricetinae , Modelos Animais de Doenças , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Leptospira interrogans/imunologia , Leptospirose/imunologia , Nanopartículas , Fatores de Transcrição/imunologia , Vacinas de DNA/imunologia
2.
Mem. Inst. Oswaldo Cruz ; 115: e190396, 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1101277

RESUMO

BACKGROUND Nanoparticles (NPs) are viable candidates as carriers of exogenous materials into cells via transfection and can be used in the DNA vaccination strategy against leptospirosis. OBJECTIVES We evaluated the efficiency of halloysite clay nanotubes (HNTs) and amine-functionalised multi-walled carbon nanotubes (NH2-MWCNTs) in facilitating recombinant LemA antigen (rLemA) expression and protecting Golden Syrian hamsters (Mesocricetus auratus) against Leptospira interrogans lethal infection. METHODS An indirect immunofluorescent technique was used to investigate the potency of HNTs and NH2-MWCNTs in enhancing the transfection and expression efficiency of the DNA vaccine in Chinese hamster ovary (CHO) cells. Hamsters were immunised with two doses of vaccines HNT-pTARGET/lemA, NH2-MWCNTs-pTARGET/lemA, pTARGET/lemA, and empty pTARGET (control), and the efficacy was determined in terms of humoral immune response and protection against a lethal challenge. FINDINGS rLemA DNA vaccines carried by NPs were able to transfect CHO cells effectively, inducing IgG immune response in hamsters (p < 0.05), and did not exhibit cytotoxic effects. Furthermore, 83.3% of the hamsters immunised with NH2-MWCNTs-pTARGET/lemA were protected against the lethal challenge (p < 0.01), and 66.7% of hamsters immunised with HNT-pTARGET/lemA survived (p < 0.05). MAIN CONCLUSIONS NH2-MWCNTs and HNTs can act as antigen carriers for mammalian cells and are suitable for DNA nanovaccine delivery.


Assuntos
Animais , Feminino , Proteínas de Bactérias/administração & dosagem , Fatores de Transcrição/administração & dosagem , Vacinas Bacterianas/administração & dosagem , Vacinas de DNA/administração & dosagem , Leptospirose/prevenção & controle , Antígenos de Bactérias/administração & dosagem , Proteínas de Bactérias/imunologia , Fatores de Transcrição/imunologia , Vacinas Bacterianas/imunologia , Cricetinae , Técnica Indireta de Fluorescência para Anticorpo , Vacinas de DNA/imunologia , Modelos Animais de Doenças , Nanopartículas , Leptospira interrogans/imunologia , Leptospirose/imunologia , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia
3.
J Med Chem ; 58(8): 3329-39, 2015 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-25811955

RESUMO

In this article we present the synthesis, characterization, and in vitro biological and biochemical activities of new chalcogenozidovudine derivatives as antioxidant (inhibition of TBARS in brain membranes and thiol peroxidase-like activity) as well as antitumoral agents in bladder carcinoma 5637. A prominent response was obtained for the selected chalcogenonucleosides, showing effective antioxidant and antitumoral activities.


Assuntos
Antineoplásicos/química , Antioxidantes/química , Calcogênios/química , Neoplasias da Bexiga Urinária/tratamento farmacológico , Zidovudina/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Antioxidantes/síntese química , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Calcogênios/síntese química , Calcogênios/farmacologia , Humanos , Masculino , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Zidovudina/síntese química , Zidovudina/farmacologia
4.
PLoS One ; 9(5): e97000, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24824737

RESUMO

Zanthoxylum rhoifolium (Rutaceae) is a plant alkaloid that grows in South America and has been used in Brazilian traditional medicine for the treatment of different health problems. The present study was designed to evaluate the antimicrobial activity of the steam bark crude methanol extract, fractions, and pure alkaloids of Z. rhoifolium. Its stem bark extracts exhibited a broad spectrum of antimicrobial activity, ranging from 12.5 to 100 µg/mL using bioautography method, and from 125 to 500 µg/mL in the microdilution bioassay. From the dichloromethane basic fraction, three furoquinoline alkaloids (1-3), and nine benzophenanthridine alkaloids (4-12) were isolated and the antimicrobial activity of the benzophenanthridine alkaloids is discussed in terms of structure-activity relationships. The alkaloid with the widest spectrum of activity was chelerythrine (10), followed by avicine (12) and dihydrochelerythrine (4). The minimal inhibitory concentrations of chelerythrine, of 1.50 µg/mL for all bacteria tested, and between 3.12 and 6.25 µg/mL for the yeast tested, show this compound to be a more powerful antimicrobial agent when compared with the other active alkaloids isolated from Z. rhoifolium. To verify the potential importance of the methylenedioxy group (ring A) of these alkaloids, chelerythrine was selected to represent the remainder of the benzophenanthridine alkaloids isolated in this work and was subjected to a demethylation reaction giving derivative 14. Compared to chelerythrine, the derivative (14) was less active against the tested bacteria and fungi. Kinetic measurements of the bacteriolytic activities of chelerythrine against the bacteria Bacillus subtilis (Gram-positive) and Escherichia coli (Gram-negative) were determined by optical density based on real time assay, suggesting that its mechanism of action is not bacteriolytic. The present study did not detect hemolytic effects of chelerythrine on erythrocytes and found a protective effect considering the decrease in TBARS and AOPP (advanced oxidized protein products) levels when compared to the control group.


Assuntos
Alcaloides/química , Anti-Infecciosos/química , Extratos Vegetais/química , Zanthoxylum , Relação Estrutura-Atividade
5.
J Nat Prod ; 76(7): 1343-50, 2013 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-23819826

RESUMO

The stereochemistry of discarines C (1) and D (2) and myrianthine A (3), three cyclopeptide alkaloids isolated from Discaria febrifuga, was determined by a combination of NMR studies of 1-3, enantioselective gas chromatography, and comparison of NMR data with those of synthetic tripeptides. For the synthesis of peptides, the nonproteinogenic amino acid 3-phenylserine was also obtained in its four diastereoisomeric forms (l and d threo, obtained by recrystallization of the diastereoisomeric tripeptide, and l and d erythro, obtained by a Mitsunobu reaction with the threo-tripeptides). The general synthetic strategy described in this paper allows the tripeptide to be obtained with the free N-terminal extremity protected or dimethylated. This strategy also allows the synthesis of the corresponding peptide with an imidazolidinone ring.


Assuntos
Alcaloides/isolamento & purificação , Peptídeos Cíclicos/isolamento & purificação , Rhamnaceae/química , Alcaloides/química , Brasil , Cromatografia Gasosa , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/química , Casca de Planta/química , Raízes de Plantas/química , Serina/análogos & derivados , Estereoisomerismo
6.
J Ethnopharmacol ; 148(2): 486-91, 2013 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-23684720

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Schinus lentiscifolius Marchand (syn. Schinus weinmannifolius Engl) is a plant native to Rio Grande do Sul (Southern Brazil) and has been used in Brazilian traditional medicine as antiseptic and antimicrobial for the treatment of many different health problems as well as to treat leucorrhea and to assist in ulcer and wound healing. Although it is a plant widely used by the population, there are no studies proving this popular use. MATERIAL AND METHODS: The crude aqueous extract, the crude neutral methanol extract, fractions prepared from this extract (n-hexane, ethyl acetate, and n-butanol), pure compounds isolated from these fractions, and derivatives were investigated in vitro for antimicrobial activities against five Gram positive bacteria: Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus pyogenes, three Gram negative bacteria: Escherichia coli, Pseudomonas aeruginosa, and Shigella sonnei, and four yeasts: Candida albicans, Candida tropicalis, Cryptococcus neoformans, and Saccharomyces cerevisiae. The isolated compound moronic acid, which is the most active, was tested against a range of other bacteria such as two Gram positive bacteria, namely, Bacillus cereus, Enterococcus spp, and six Gram negative bacteria, namely, Burkholderia cepacia, Providencia stuartii, Morganella morganii, Enterobacter cloacae, Enterobacter aerogenes, and Proteus mirabilis. RESULTS: The leaf aqueous extract (decoction) of Schinus lentiscifolius showed a broad spectrum of antibacterial activity, ranging from 125 to 250 µg/ml (MIC) against the tested bacteria and fungi. The n-hexane extract, despite being very little active against bacteria, showed an excellent antifungal activity, especially against Candida albicans (MIC=25 µg/ml), Candida tropicalis (MIC=15.5 µg/ml), and Cryptococcus neoformans, (MIC=15.5 µg/ml). From the acetate fraction (the most active against bacteria), compounds 1-6 were isolated: nonadecanol (1), moronic acid (2), gallic acid methyl ester (3), gallic acid (4), quercetin (5) and quercitrin (6). The minimal inhibitory concentration (MIC) of moronic acid between 1.5 and 3 µg/ml against most of the tested bacteria shows that it is one of the metabolites responsible for the antibacterial activity of Schinus lentiscifolius. CONCLUSION: The antimicrobial activity and some constituents of Schinus lentiscifolius are reported for the first time. The results of the present study provide scientific basis for the popular use of Schinus lentiscifolius for a number of different health problems.


Assuntos
Anacardiaceae/química , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Extratos Vegetais/farmacologia , Antibacterianos/química , Antifúngicos/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Medicina Tradicional/métodos , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Folhas de Planta/química , Leveduras/efeitos dos fármacos
7.
J Nat Prod ; 75(6): 1220-2, 2012 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-22680778

RESUMO

The absolute configuration of franganine (1), a cyclopeptide alkaloid isolated from the methanol root bark extract of Discaria americana, was established on the basis of detailed NMR spectroscopic data and X-ray diffraction analysis of its salt (2).


Assuntos
Alcaloides/química , Peptídeos Cíclicos/química , Brasil , Cristalografia por Raios X , Conformação Molecular , Estrutura Molecular , Casca de Planta/química , Rhamnaceae/química , Sais
8.
Phytother Res ; 26(10): 1472-5, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22275311

RESUMO

The phenylpropanoid glycoside verbascoside [2-(3,4-dihydroxyphenylethyl)-1-O-α-L-rhamnopyranosyl-(1→3)-ß-D-(4-O-caffeyl)-glucopyranoside] (1) has been isolated as the main constituent of the crude extract of Buddleja brasiliensis Jacq. ex Spreng from Southern Brazil. The crude extract, main fractions and the compound 1 were evaluated for inhibition of the enzymes acetylcholinesterase (AChE), dipeptidyl peptidase-IV (DPP-IV) and prolyl oligopeptidase (POP). Compound 1 showed weak activity against DPP-IV with an IC(50) >> 150 µM and was inactive against AChE, with a pMIQ determined by bioautography of 9.6. In contrast, 1 displayed significant inhibition of POP in a dose-dependent manner with an IC(50) value of 1.3 ± 0.2 µM, similar to the positive control, baicalin, with a POP IC(50) of 12 ± 3 µM.


Assuntos
Buddleja/química , Glucosídeos/química , Fenóis/química , Serina Endopeptidases/química , Inibidores de Serina Proteinase/química , Fracionamento Químico , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Dipeptidil Peptidase IV/química , Inibidores da Dipeptidil Peptidase IV/isolamento & purificação , Glucosídeos/isolamento & purificação , Concentração Inibidora 50 , Fenóis/isolamento & purificação , Extratos Vegetais/química , Prolil Oligopeptidases , Inibidores de Serina Proteinase/isolamento & purificação
9.
Phytochemistry ; 72(8): 804-9, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21420695

RESUMO

Scutianene E (1), 3,4,28-tris-epi-scutiaene E (2), 28-epi-scutianene E (3) and scutianene L (4), four neutral cyclopeptide alkaloids, were isolated from Scutia buxifolia Reiss, together with four known cyclopeptide alkaloids, scutianines B, C, D and E. Scutianenes 1-3 are diastereoisomeric compounds, with 3-hydroxyleucine as a ß-hydroxy amino acid unit, which is connected to the styryl fragment via an ether bridge, ß-phenylserine, as a common ring-bonded amino acid residue. Attached to the amino group of ß-hydroxyamino acid is a side chain [trans-CH=CH-Ph]. The structures of the peptides were elucidated by means of spectroscopic analysis, including extensive 2D NMR studies. The stereochemistry for the diastereomeric 3,4,28-tris-epi-scutiaene E and 28-epi-scutianene E was confirmed by X-ray diffraction analysis of their O-acetyl derivatives.


Assuntos
Alcaloides/isolamento & purificação , Peptídeos Cíclicos/isolamento & purificação , Rhamnaceae/química , Alcaloides/química , Cristalografia por Raios X , Conformação Molecular , Estrutura Molecular , Peptídeos Cíclicos/química
11.
J Nat Prod ; 72(4): 608-12, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19231884

RESUMO

The analgesic potential of six 14-membered-ring cyclopeptide alkaloids, namely, franganine (1), discarine B (2), scutianines B (3), C (4), and D (5), and adouetine X (6), have been investigated. Among the compounds tested, only franganine (1) and adouetine X (6) produced antinociceptive effects in a mouse model of acute pain, without inducing undesirable side effects. Furthermore, compound 6 also exhibited a pronounced analgesic effect in a chronic neuropathic pain model in mice. It has been found that adouetine X (6) can decrease the activities of Ca(2+)-ATPase and Na(+)/K(+)-ATPase in vitro. Thus, the present findings have demonstrated that adouetine X (6) is a promising analgesic agent.


Assuntos
Alcaloides/farmacologia , Analgésicos/isolamento & purificação , Analgésicos/farmacologia , ATPases Transportadoras de Cálcio/antagonistas & inibidores , Malvaceae/química , Peptídeos Cíclicos/isolamento & purificação , Peptídeos Cíclicos/farmacologia , Plantas Medicinais/química , Rhamnaceae/química , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Alcaloides/química , Analgésicos/química , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Estrutura Molecular , Peptídeos Cíclicos/química
12.
Phytochemistry ; 66(21): 2571-6, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16226284

RESUMO

The present study reports a cyclopeptide alkaloid, scutianine M, isolated from the methanolic root bark extract of Scutia buxifolia Reiss (Rhamnaceae) along with six known compounds, scutianines-B, -C, -D, -E, -F, and scutianene D. Its structure was established on the basis of spectroscopic analyses, including application of 2D NMR spectroscopic techniques. As part of a study of the bioactive compounds of medicinal plants from southern Brazil, we also compared the antimicrobial activity of the isolated compounds towards Gram (+), Gram (-) bacteria, and yeasts.


Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Peptídeos Cíclicos/isolamento & purificação , Peptídeos Cíclicos/farmacologia , Rhamnaceae/química , Alcaloides/química , Antibacterianos/química , Bactérias/efeitos dos fármacos , Estrutura Molecular , Peptídeos Cíclicos/química , Casca de Planta/química , Raízes de Plantas/química
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