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1.
Molecules ; 28(3)2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36770886

RESUMO

In recent years, lycopene has been highlighted due to its antioxidant and anti-inflammatory properties, associated with a beneficial effect on human health. The aim of this study was to advance the studies of antioxidant and anti-inflammatory mechanisms on human keratinocytes cells (HaCaT) of a self-emulsifying drug delivery system (SEDDS) loaded with lycopene purified from red guava (nanoLPG). The characteristics of nanoLPG were a hydrodynamic diameter of 205 nm, a polydispersity index of 0.21 and a zeta potential of -20.57, providing physical stability for the nanosystem. NanoLPG demonstrated antioxidant capacity, as shown using the ORAC methodology, and prevented DNA degradation (DNA agarose). Proinflammatory activity was evaluated by quantifying the cytokines TNF-α, IL-6 and IL-8, with only IL-8 showing a significant increase (p < 0.0001). NanoLPG showed greater inhibition of the tyrosinase and elastase enzymes, involved in the skin aging process, compared to purified lycopene (LPG). In vitro treatment for 24 h with 5.0 µg/mL of nanoLPG did not affect the viability of HaCaT cells. The ultrastructure of HaCaT cells demonstrated the maintenance of morphology. This contrasts with endoplasmic reticulum stresses and autophagic vacuoles when treated with LPG after stimulation or not with LPS. Therefore, the use of lycopene in a nanoemulsion may be beneficial in strategies and products associated with skin health.


Assuntos
Antioxidantes , Interleucina-8 , Humanos , Licopeno , Antioxidantes/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Anti-Inflamatórios/farmacologia , DNA
2.
J Nat Prod ; 85(12): 2695-2705, 2022 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-36508333

RESUMO

In this study, we report the isolation, characterization, and synthesis of the peptide BmT-2 belonging to the tryptophyllins family, isolated from the venom of the snake Bothrops moojeni. This is the first time a tryptophyllin is identified in snake venom. We tested whether BmT-2 had cytotoxic effects and antioxidant activity in a set of experiments that included both in vitro and cell-based assays. BmT-2 presented a radical scavenging activity toward ABTS• and AAPH-derived radicals. BmT-2 protected fluorescein, DNA molecules, and human red blood cells (RBCs) from free radicals generated by the thermal decomposition of AAPH. The novel tryptophyllin was not toxic in cell viability tests, where it (up to 0.4 mg/mL) did not cause hemolysis of human RBCs and did not cause significant loss of cell viability, showing a CC50 > 1.5 mM for cytotoxic effects against SK-N-BE(2) neuroblastoma cells. BmT-2 prevented the arsenite-induced upregulation of Nrf2 in Neuro-2a neuroblasts and the phorbol myristate acetate-induced overgeneration of reactive oxygen species and reactive nitrogen species in SK-N-BE(2) neuroblastoma cells. Electronic structure calculations and full atomistic reactive molecular dynamics simulations revealed the relevant contribution of aromatic residues in BmT-2 to its antioxidant properties. Our study presents a novel peptide classified into the family of the tryptophyllins, which has been reported exclusively in amphibians. Despite the promising results on its antioxidant activity and low cytotoxicity, the mechanisms of action of BmT-2 still need to be further elucidated.


Assuntos
Bothrops , Venenos de Crotalídeos , Neuroblastoma , Fármacos Neuroprotetores , Animais , Humanos , Antioxidantes/farmacologia , Venenos de Crotalídeos/química , Venenos de Crotalídeos/farmacologia , Peptídeos , Venenos de Serpentes
3.
Proc Biol Sci ; 288(1962): 20211531, 2021 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-34753356

RESUMO

In addition to the morphophysiological changes experienced by amphibians during metamorphosis, they must also deal with a different set of environmental constraints when they shift from the water to the land. We found that Pithecopus azureus secretes a single peptide ([M + H]+ = 658.38 Da) at the developmental stage that precedes the onset of terrestrial behaviour. De novo peptide and cDNA sequencing revealed that the peptide, named PaT-2, is expressed in tandem and is a member of the tryptophyllins family. In silico studies allowed us to identify the position of reactive sites and infer possible antioxidant mechanisms of the compounds. Cell-based assays confirmed the predicted antioxidant activity in mammalian microglia and neuroblast cells. The potential neuroprotective effect of PaT-2 was further corroborated in FRET-based live cell imaging assays, where the peptide prevented lipopolysaccharide-induced ROS production and glutamate release in human microglia. In summary, PaT-2 is the first peptide expressed during the ontogeny of P. azureus, right before the metamorphosing froglet leaves the aquatic environment to occupy terrestrial habitats. The antioxidant activity of PaT-2, predicted by in silico analyses and confirmed by cell-based assays, might be relevant for the protection of the skin of P. azureus adults against increased O2 levels and UV exposure on land compared with aquatic environments.


Assuntos
Antioxidantes , Água , Animais , Antioxidantes/análise , Anuros/fisiologia , Humanos , Mamíferos , Peptídeos/análise , Pele , Água/análise
4.
J Nat Prod ; 84(6): 1787-1798, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34077221

RESUMO

Snake venoms are important sources of bioactive molecules, including those with antiparasitic activity. Cathelicidins form a class of such molecules, which are produced by a variety of organisms. Batroxicidin (BatxC) is a cathelicidin found in the venom of the common lancehead (Bothrops atrox). In the present work, BatxC and two synthetic analogues, BatxC(C-2.15Phe) and BatxC(C-2.14Phe)des-Phe1, were assessed for their microbicidal activity. All three peptides showed a broad-spectrum activity on Gram-positive and -negative bacteria, as well as promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. Circular dichroism (CD) and nuclear magnetic resonance (NMR) data indicated that the three peptides changed their structure upon interaction with membranes. Biomimetic membrane model studies demonstrated that the peptides exert a permeabilization effect in prokaryotic membranes, leading to cell morphology distortion, which was confirmed by atomic force microscopy (AFM). The molecules considered in this work exhibited bactericidal and leishmanicidal activity at low concentrations, with the AFM data suggesting membrane pore formation as their mechanism of action. These peptides stand as valuable prototype drugs to be further investigated and eventually used to treat bacterial and protozoal infections.


Assuntos
Antibacterianos/farmacologia , Peptídeos Antimicrobianos/farmacologia , Antiprotozoários/farmacologia , Bothrops , Venenos de Serpentes/química , Sequência de Aminoácidos , Animais , Antibacterianos/química , Peptídeos Antimicrobianos/química , Antiprotozoários/química , Catelicidinas , Células Cultivadas , Leishmania/efeitos dos fármacos , Macrófagos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , América do Sul
5.
Int J Mol Sci ; 20(14)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340580

RESUMO

Pseudomonas aeruginosa and Staphylococcus aureus are two major pathogens involved in a large variety of infections. Their co-occurrence in the same site of infection has been frequently reported and is linked to enhanced virulence and difficulty of treatment. Herein, the antimicrobial and antibiofilm activities of an intragenic antimicrobial peptide (IAP), named Hs02, which was uncovered from the human unconventional myosin 1H protein, were investigated against several P. aeruginosa and S. aureus strains, including multidrug-resistant (MDR) isolates. The antibiofilm activity was evaluated on single- and dual-species biofilms of P. aeruginosa and S. aureus. Moreover, the effect of peptide Hs02 on the membrane fluidity of the strains was assessed through Laurdan generalized polarization (GP). Minimum inhibitory concentration (MIC) values of peptide Hs02 ranged from 2 to 16 µg/mL against all strains and MDR isolates. Though Hs02 was not able to hamper biofilm formation by some strains at sub-MIC values, it clearly affected 24 h preformed biofilms, especially by reducing the viability of the bacterial cells within the single- and dual-species biofilms, as shown by confocal laser scanning microscopy (CLSM) and atomic force microscopy (AFM) images. Laurdan GP values showed that Hs02 induces membrane rigidification in both P. aeruginosa and S. aureus. Peptide Hs02 can potentially be a lead for further improvement as an antibiofilm agent.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Biofilmes/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , 2-Naftilamina/análogos & derivados , 2-Naftilamina/química , Antibacterianos/isolamento & purificação , Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Biofilmes/crescimento & desenvolvimento , Contagem de Colônia Microbiana , Meios de Cultura/química , Humanos , Lauratos/química , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Staphylococcus aureus/crescimento & desenvolvimento
6.
Int J Mol Sci ; 19(6)2018 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-29921756

RESUMO

Schistosomiasis, caused by helminth flatworms of the genus Schistosoma, is an infectious disease mainly associated with poverty that affects millions of people worldwide. Since treatment for this disease relies only on the use of praziquantel, there is an urgent need to identify new antischistosomal drugs. Piplartine is an amide alkaloid found in several Piper species (Piperaceae) that exhibits antischistosomal properties. The aim of this study was to evaluate the structure­function relationship between piplartine and its five synthetic analogues (19A, 1G, 1M, 14B and 6B) against Schistosoma mansoni adult worms, as well as its cytotoxicity to mammalian cells using murine fibroblast (NIH-3T3) and BALB/cN macrophage (J774A.1) cell lines. In addition, density functional theory calculations and in silico analysis were used to predict physicochemical and toxicity parameters. Bioassays revealed that piplartine is active against S. mansoni at low concentrations (5⁻10 µM), but its analogues did not. In contrast, based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, piplartine exhibited toxicity in mammalian cells at 785 µM, while its analogues 19A and 6B did not reduce cell viability at the same concentrations. This study demonstrated that piplartine analogues showed less activity against S. mansoni but presented lower toxicity than piplartine.


Assuntos
Anti-Helmínticos/farmacologia , Piperidonas/farmacologia , Extratos Vegetais/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Células 3T3 , Animais , Anti-Helmínticos/química , Anti-Helmínticos/toxicidade , Cricetinae , Fibroblastos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Piper/química , Piperidonas/química , Piperidonas/toxicidade , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Relação Quantitativa Estrutura-Atividade , Caramujos
7.
J Nat Prod ; 78(7): 1495-504, 2015 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-26107622

RESUMO

Eight new peptides were isolated from the skin secretion of the frog Leptodactylus pustulatus and their amino acid sequences determined by de novo sequencing and by cDNA cloning. Structural similarities between them and other antimicrobial peptides from the skin secretion of Leptodactylus genus frogs were found. Ocellatins-PT1 to -PT5 (25 amino acid residues) are amidated at the C-terminus, while ocellatins-PT6 to -PT8 (32 amino acid residues) have free carboxylates. Antimicrobial activity, hemolytic tests, and cytotoxicity against a murine fibroblast cell line were investigated. All peptides, except for ocellatin-PT2, have antimicrobial activity against at least one Gram-negative strain. Ocellatin-PT8 inhibited the growth of Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Salmonella choleraesuis strains with MICs in the 60-240 µM range. No significant effect was observed in human erythrocytes and in a murine fibroblast cell line after exposure to the peptides at MICs. A comparison between sequences obtained by both direct HPLC-MS de novo sequencing and cDNA cloning demonstrates the secretion of mature peptides derived from a pre-pro-peptide structure.


Assuntos
Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Peptídeos Catiônicos Antimicrobianos/farmacologia , Ranidae/metabolismo , Pele/metabolismo , Sequência de Aminoácidos , Animais , Peptídeos Catiônicos Antimicrobianos/sangue , Peptídeos Catiônicos Antimicrobianos/química , Eritrócitos/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Estrutura Molecular , Células NIH 3T3 , Ranidae/genética , Salmonella/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
8.
Drug Dev Res ; 76(3): 143-51, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25959135

RESUMO

Long-term use nonsteroidal anti-inflammatory drug is associated with gastrointestinal (GI) lesion formation. The aim of this study was to investigate the protective activity of cashew gum (CG), a complex heteropolysaccharide extracted from Anacardium occidentale on naproxen (NAP)-induced GI damage. Male Wistar rats were pretreated with vehicle or CG (1, 3, 10, and 30 mg/kg, p.o.) twice daily for 2 days; after 1 h, NAP (80 mg/kg, p.o.) was administered. The rats were euthanized on the 2nd day of treatment, 4 h after NAP administration. Stomach lesions were measured using digital calipers. The medial small intestine was used for the evaluation of macroscopic lesion scores. Samples of the stomach and the intestine were used for histological evaluation, and assays for glutathione (GSH), malonyldialdehyde (MDA), and myeloperoxidase (MPO). Additional rats were used to measure gastric mucus and secretion. Pretreatment with CG reduced the macroscopic and microscopic damage induced by NAP. CG significantly attenuated NAP-induced alterations in MPO, GSH, and MDA levels. Furthermore, CG returned adherent mucus levels to normal values. These results suggest that CG has a protective effect against GI damage via mechanisms that involve the inhibition of inflammation and increasing the amount of adherent mucus in mucosa.


Assuntos
Anacardium , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/prevenção & controle , Naproxeno/efeitos adversos , Gomas Vegetais/uso terapêutico , Polissacarídeos/uso terapêutico , Animais , Gastroenteropatias/patologia , Masculino , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Gomas Vegetais/isolamento & purificação , Polissacarídeos/isolamento & purificação , Ratos , Ratos Wistar
9.
J Nanobiotechnology ; 12: 36, 2014 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-25223611

RESUMO

BACKGROUND: Type I collagen is an abundant natural polymer with several applications in medicine as matrix to regenerate tissues. Silver nanoparticles is an important nanotechnology material with many utilities in some areas such as medicine, biology and chemistry. The present study focused on the synthesis of silver nanoparticles (AgNPs) stabilized with type I collagen (AgNPcol) to build a nanomaterial with biological utility. Three formulations of AgNPcol were physicochemical characterized, antibacterial activity in vitro and cell viability assays were analyzed. AgNPcol was characterized by means of the following: ultraviolet-visible spectroscopy, dynamic light scattering analysis, Fourier transform infrared spectroscopy, atomic absorption analysis, transmission electron microscopy and of X-ray diffraction analysis. RESULTS: All AgNPcol showed spherical and positive zeta potential. The AgNPcol at a molar ratio of 1:6 showed better characteristics, smaller hydrodynamic diameter (64.34 ± 16.05) and polydispersity index (0.40 ± 0.05), and higher absorbance and silver reduction efficiency (0.645 mM), when compared with the particles prepared in other mixing ratios. Furthermore, these particles showed antimicrobial activity against both Staphylococcus aureus and Escherichia coli and no toxicity to the cells at the examined concentrations. CONCLUSIONS: The resulted particles exhibited favorable characteristics, including the spherical shape, diameter between 64.34 nm and 81.76 nm, positive zeta potential, antibacterial activity, and non-toxicity to the tested cells (OSCC).


Assuntos
Antibacterianos/farmacologia , Colágeno Tipo I/farmacologia , Nanopartículas Metálicas/química , Prata/farmacologia , Antibacterianos/química , Linhagem Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Química Sintética , Colágeno Tipo I/administração & dosagem , Colágeno Tipo I/química , Avaliação Pré-Clínica de Medicamentos/métodos , Difusão Dinâmica da Luz , Escherichia coli/efeitos dos fármacos , Humanos , Nanopartículas Metálicas/administração & dosagem , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Transmissão , Prata/administração & dosagem , Prata/química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Difração de Raios X
10.
J Nanosci Nanotechnol ; 14(6): 4519-28, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24738423

RESUMO

Schistosomiasis is a neglected tropical disease caused by blood flukes of the genus Schistosoma. This disease control has been widely made by praziquantel-reference drug, but resistance to this drug has already been found. There has been the finding of an imidazole alkaloid in jaborandi leaves-epiisopiloturine, which has known activity against adult, young and egg forms of Schistosoma mansoni. This alkaloid is an apolar molecule with difficult solubility; therefore, the liposomal structure of epiisopiloturine was proposed. Liposomes are carrying structures of drugs that may enhance solubility of compounds such as epiisopiloturine. In this work, we report in vitro epiisopiloturine-loaded liposomes effect formed by different concentrations of lipids 9:1 (weight ratio) dipalmitoylphosphatidylcholine:cholesterol and 8:2 (weight ratio) dipalmitoylphosphatidylcholine:cholesterol. Results have showed that epiisopiloturine extraction and isolation have been successful through high-performance liquid chromatography-HPLC and its purity confirmed through mass spectrometry has showed 287 Da molecular mass. Formulations from 9:1 DPPC:cholesterol and 8:2 DPPC:cholesterol with loaded EPI (300 microg/ml) have killed parasites at 100% after incubation 96 h and 120 h, respectively. Confocal microscopy employed to observe morphological alterations in the tegument of adult form of Schistosoma mansoni. Details from interaction, between epiisopiloturine and liposome, have been achieved by semi-empirical AM1 calculations, which have showed that epiisopiloturine inside is more stable than the outside form, at least 10 kcal. This is first time that schistosomicidal activity has been reported for epiisopiloturine-loaded into liposome.


Assuntos
4-Butirolactona/análogos & derivados , Imidazóis/síntese química , Imidazóis/farmacologia , Lipossomos/química , Nanocápsulas/administração & dosagem , Schistosoma mansoni/efeitos dos fármacos , Schistosoma mansoni/fisiologia , 4-Butirolactona/síntese química , 4-Butirolactona/farmacologia , Animais , Anti-Helmínticos/síntese química , Anti-Helmínticos/farmacologia , Teste de Materiais , Nanocápsulas/química , Schistosoma mansoni/anatomia & histologia , Resultado do Tratamento
11.
Nanomedicine ; 10(2): 483-90, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24096030

RESUMO

Leishmaniasis is one of the most serious diseases in the world and can be lethal if untreated. This is especially the case for visceral leishmaniasis, which is commonly caused by Leishmania (L.) infantum and for which available medication is still inadequate. A recently described antimicrobial peptide DRS 01 has been reported to kill L. infantum promastigotes, but nothing is known about its mode of action or effect on the cell. In this paper we report the visualization of the interaction between DRS 01 and L. infantum promastigotes using two high resolution microscopic techniques: atomic force microscopy and scanning electron microscopy. The results show considerable morphological changes at and above the IC50 in the treated cells. Both membrane damage and flagella alterations were observed. The results strongly suggest a membrane-directed action for DRS 01 on the Leishmania species studied. FROM THE CLINICAL EDITOR: In this paper, the effects of DRS 01, an antimicrobial peptide, is studied in Leishmania infantum using atomic force microscopy as well as standard scanning electron microscopy techniques, with the conclusion of a membrane-based effect by DRS 01 on the parasites.


Assuntos
Proteínas de Anfíbios/química , Peptídeos Catiônicos Antimicrobianos/química , Antiprotozoários/uso terapêutico , Leishmania infantum/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Proteínas de Anfíbios/isolamento & purificação , Animais , Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Membrana Celular/parasitologia , Flagelos , Humanos , Concentração Inibidora 50 , Leishmaniose Visceral/parasitologia
12.
Pharmaceutics ; 16(2)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38399250

RESUMO

The potential emergence of zoonotic diseases has raised significant concerns, particularly in light of the recent pandemic, emphasizing the urgent need for scientific preparedness. The bioprospection and characterization of new molecules are strategically relevant to the research and development of innovative drugs for viral and bacterial treatment and disease management. Amphibian species possess a diverse array of compounds, including antimicrobial peptides. This study identified the first bioactive peptide from Salamandra salamandra in a transcriptome analysis. The synthetic peptide sequence, which belongs to the defensin family, was characterized through MALDI TOF/TOF mass spectrometry. Molecular docking assays hypothesized the interaction between the identified peptide and the active binding site of the spike WT RBD/hACE2 complex. Although additional studies are required, the preliminary evaluation of the antiviral potential of synthetic SS-I was conducted through an in vitro cell-based SARS-CoV-2 infection assay. Additionally, the cytotoxic and hemolytic effects of the synthesized peptide were assessed. These preliminary findings highlighted the potential of SS-I as a chemical scaffold for drug development against COVID-19, hindering viral infection. The peptide demonstrated hemolytic activity while not exhibiting cytotoxicity at the antiviral concentration.

13.
J Nat Prod ; 76(6): 1071-7, 2013 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-23734744

RESUMO

The aim of this study was to investigate the antinociceptive and anti-inflammatory activities of epiisopiloturine (1), an imidazole alkaloid found in the leaves of Pilocarpus microphyllus. The anti-inflammatory activity of 1 was evaluated using several agents that induce paw edema and peritonitis in Swiss mice. Paw tissue and peritoneal fluid samples were obtained to determine myeloperoxidase (MPO) activity or tumor necrosis factor (TNF)-α and interleukin (IL)-1ß levels. The antinociceptive activity was evaluated by acetic acid-induced writhing, the hot plate test, and pain induction using formalin. Compared to vehicle treatment, pretreatment with 1 (0.1, 0.3, and 1 mg/kg, ip) of mice significantly reduced carrageenan-induced paw edema (p < 0.05). Furthermore, compound 1 at a dose of 1 mg/kg effectively inhibited edema induced by dextran sulfate, serotonin, and bradykinin, but had no effect on histamine-induced edema. The administration of 1 (1 mg/kg) following carrageenan-induced peritonitis reduced total and differential peritoneal leukocyte counts and also carrageenan-induced paw MPO activity and TNF-α and IL-1ß levels in the peritoneal cavity. Pretreatment with 1 also reduced acetic acid-induced writhing and inhibited the first and second phases of the formalin test, but did not alter response latency in the hot plate test. Pretreatment with naloxone reversed the antinociceptive effect of 1.


Assuntos
4-Butirolactona/análogos & derivados , Alcaloides/farmacologia , Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Imidazóis/farmacologia , Pilocarpus/química , 4-Butirolactona/química , 4-Butirolactona/farmacologia , Alcaloides/sangue , Alcaloides/química , Analgésicos/sangue , Analgésicos/química , Animais , Anti-Inflamatórios/sangue , Anti-Inflamatórios/química , Brasil , Imidazóis/química , Masculino , Camundongos , Estrutura Molecular , Neutrófilos/efeitos dos fármacos , Medição da Dor , Peroxidase/sangue , Peroxidase/metabolismo
14.
Int J Mol Sci ; 14(3): 4969-81, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23455467

RESUMO

The present study describes the development of a green synthesis of silver nanoparticles reduced and stabilized by exuded gum from Anacardium occidentale L. and evaluates in vitro their antibacterial and cytotoxic activities. Characterization of cashew gum-based silver nanoparticles (AgNPs) was carried out based on UV-Vis spectroscopy, transmission electron microscopy and dynamic light scattering analysis which revealed that the synthesized silver nanoparticles were spherical in shape, measuring about 4 nm in size with a uniform dispersal. AgNPs presented antibacterial activity, especially against Gram-negative bacteria, in concentrations where no significant cytotoxicity was observed.

15.
Molecules ; 18(6): 7058-70, 2013 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-23774944

RESUMO

Antimicrobial peptides (AMPs) from the dermaseptin and phylloseptin families were isolated from the skin secretion of Phyllomedusa nordestina, a recently described amphibian species from Northeastern Brazil. One dermaseptin and three phylloseptins were chosen for solid phase peptide synthesis. The antiprotozoal and antimicrobial activities of the synthetic peptides were determined, as well as their cytotoxicity in mouse peritoneal cells. AMPs are being considered as frameworks for the development of novel drugs inspired by their mechanism of action.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Peptídeos Catiônicos Antimicrobianos/farmacologia , Pele/metabolismo , Proteínas de Anfíbios/química , Proteínas de Anfíbios/metabolismo , Proteínas de Anfíbios/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Antiprotozoários/química , Antiprotozoários/farmacologia , Anuros , Macrófagos/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
16.
Antibiotics (Basel) ; 12(3)2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36978294

RESUMO

Antimicrobial resistance is currently one of the greatest threats to global health, food security, and development. In this aspect, medicinal plants have been studied to support the development of viable alternatives to prevent and treat infectious diseases. This study aimed to perform a review of the literature comprising the antimicrobial activity of vegetable species from Brazilian biomes. We selected 67 original scientific publications about extracts, fractions, or isolated molecules from plants in the Brazilian biomes, published between 2016 and 2020 in Pubmed, ScienceDirect, and Scielo. Data demonstrated that 98 plant species, especially collected in the Cerrado, Atlantic Forest, and Caatinga biomes, were tested against 40 fungi and 78 bacterial strains. Bioactive fractions of Eucalyptus globulus methanolic stump wood extract were active against Candida albicans and C. tropicalis (MIC 2.50 µg/mL). The catechin purified from Banisteriopsis argyrophylla leaves had activity against C. glabrata (MIC 2.83 µg/mL) and ethanolic extract obtained from Caryocar coriaceum bark and fruit pulp exhibited MIC of 4.1 µg/mL on Microsporum canis. For bacteria, compounds isolated from the dichloromethane extract of Peritassa campestris, lectin extracted from a saline extract of Portulaca elatior and essential oils of Myrciaria pilosa exhibited significant effect against Bacillus megaterium (MIC 0.78 µg/mL), Pseudomonas aeruginosa (MIC 4.06 µg/mL) and Staphylococcus aureus strains (MIC 5.0 µg/mL), respectively. The findings support the antimicrobial and bioeconomic potential of plants from Brazilian biodiversity and their promising health applications.

17.
Pharmaceutics ; 15(7)2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37514049

RESUMO

Amphibian secretions have been extensively investigated for the production of bioactive molecules. Salamandrin-I is an antioxidant peptide, isolated from the skin secretion of the fire salamander, that has induced no toxicity in microglia or erythrocytes. Importantly, the administration of antioxidants may constitute an adequate therapeutic approach to cancer treatment. Here, with the purpose of better characterizing the therapeutic potential of salamandrin-I, we investigated whether this antioxidant peptide also exerts anticancer activity, using the human leukemia cell line HL-60 as a cancer model. Salamandrin-I treatment induced a significant reduction in HL-60 proliferation, which was accompanied by cell cycle arrest. Furthermore, the peptide-induced cell death showed a significant increase in the LDH release in HL-60 cells. The cellular toxicity exerted by salamandrin-I is possibly related to pyroptosis, since the HL-60 cells showed loss of mitochondrial membrane potential and hyperexpression of inflammasome components following the peptide treatment. This is the first demonstration of the anticancer potential of the salamandrin-I peptide. Such results are important, as they offer relevant insights into the field of cancer therapy and allow the design of future bioactive molecules using salamandrin-I as a template.

18.
Biochim Biophys Acta Gen Subj ; 1867(1): 130265, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36280021

RESUMO

BACKGROUND: Some cationic and amphiphilic α-helical segments of proteins adsorb to prokaryotic membranes when synthesized as individual polypeptide sequences, resulting in broad and potent antimicrobial activity. However, amphiphilicity, a determinant physicochemical property for peptide-membrane interactions, can also be observed in some ß-sheets. METHODS: The software Kamal was used to scan the human reference proteome for short (7-11 amino acid residues) cationic and amphiphilic protein segments with the characteristic periodicity of ß-sheets. Some of the uncovered peptides were chemically synthesized, and antimicrobial assays were conducted. Biophysical techniques were used to probe the molecular interaction of one peptide with phospholipid vesicles, lipopolysaccharides (LPS) and the bacterium Escherichia coli. RESULTS: Thousands of compatible segments were found in human proteins, five were synthesized, and three presented antimicrobial activity in the micromolar range. Hs10, a nonapeptide fragment of the Complement C3 protein, could inhibit only the growth of tested Gram-negative microorganisms, presenting also little cytotoxicity to human fibroblasts. Hs10 interacted with LPS while transitioning from an unstructured segment to a ß-sheet and increased the hydrodynamic radius of LPS particles. This peptide also promoted morphological alterations in E. coli cells. CONCLUSIONS: Data presented herein introduce yet another molecular template to probe proteins in search for encrypted membrane-active segments and demonstrates that, using this approach, short peptides with low cytotoxicity and high selectivity to prokaryotic cells might be obtained. GENERAL SIGNIFICANCE: This work widens the biotechnological potential of the human proteome as a source of antimicrobial peptides with application in human health.


Assuntos
Anti-Infecciosos , Escherichia coli , Humanos , Escherichia coli/metabolismo , Peptídeos Antimicrobianos , Lipopolissacarídeos/farmacologia , Proteoma , Bactérias Gram-Negativas/metabolismo , Peptídeos/química
19.
J Pept Sci ; 17(10): 700-7, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21805539

RESUMO

This article addresses the interactions of the synthetic antimicrobial peptide dermaseptin 01 (GLWSTIKQKGKEAAIAAA- KAAGQAALGAL-NH(2) , DS 01) with phospholipid (PL) monolayers comprising (i) a lipid-rich extract of Leishmania amazonensis (LRE-La), (ii) zwitterionic PL (dipalmitoylphosphatidylcholine, DPPC), and (iii) negatively charged PL (dipalmitoylphosphatidylglycerol, DPPG). The degree of interaction of DS 01 with the different biomembrane models was quantified from equilibrium and dynamic liquid-air interface parameters. At low peptide concentrations, interactions between DS 01 and zwitterionic PL, as well as with the LRE-La monolayers were very weak, whereas with negatively charged PLs the interactions were stronger. For peptide concentrations above 1 µg/ml, a considerable expansion of negatively charged monolayers occurred. In the case of DPPC, it was possible to return to the original lipid area in the condensed phase, suggesting that the peptide was expelled from the monolayer. However, in the case of DPPG, the average area per lipid molecule in the presence of DS 01 was higher than pure PLs even at high surface pressures, suggesting that at least part of DS 01 remained incorporated in the monolayer. For the LRE-La monolayers, DS 01 also remained in the monolayer. This is the first report on the antiparasitic activity of AMPs using Langmuir monolayers of a natural lipid extract from L. amazonensis.


Assuntos
Proteínas de Anfíbios/química , Peptídeos Catiônicos Antimicrobianos/química , Antiprotozoários/química , Leishmania/efeitos dos fármacos , Fosfolipídeos/metabolismo , Sequência de Aminoácidos , Proteínas de Anfíbios/farmacocinética , Anti-Infecciosos/química , Peptídeos Catiônicos Antimicrobianos/farmacocinética , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Leishmania/metabolismo , Membranas Artificiais , Modelos Biológicos
20.
Front Pharmacol ; 12: 810821, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35095522

RESUMO

Urodele amphibians (∼768 spp.), salamanders and newts, are a rich source of molecules with bioactive properties, especially those isolated from their skin secretions. These include pharmacological attributes, such as antimicrobial, antioxidant, vasoactive, immune system modulation, and dermal wound healing activities. Considering the high demand for new compounds to guide the discovery of new drugs to treat conventional and novel diseases, this review summarizes the characteristics of molecules identified in the skin of urodele amphibians. We describe urodele-derived peptides and alkaloids, with emphasis on their biological activities, which can be considered new scaffolds for the pharmaceutical industry. Although much more attention has been given to anurans, bioactive molecules produced by urodeles have the potential to be used for biotechnological purposes and stand as viable alternatives for the development of therapeutic agents.

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