RESUMO
Alicyclobacillus spp. is the cause of great concern for the food industry due to their spores' resistance (thermal and chemical) and the spoilage potential of some species. Despite this, not all Alicyclobacillus strains can spoil fruit juices. Thus, this study aimed to identify Alicyclobacillus spp. strains isolated from fruit-based products produced in Argentina, Brazil, and Italy by DNA sequencing. All Alicyclobacillus isolates were tested for guaiacol production by the peroxidase method. Positive strains for guaiacol production were individually inoculated at concentration of 103 CFU/mL in 10 mL of orange (pH 3.90) and apple (pH 3.50) juices adjusted to 11°Brix, following incubation at 45 °C for at least 5 days to induce the production of the following spoilage compounds: Guaiacol, 2,6-dichlorophenol (2,6-DCP) and 2,6-dibromophenol (2,6-DBP). The techniques of micro-solid phase extraction by headspace (HS-SPME) and gas-chromatography with mass spectrometry (GC-MS) were used to identify and quantify the spoilage compounds. All GC-MS data was analyzed by principal component analysis (PCA). The effects of different thermal shock conditions on the recovery of Alicyclobacillus spores inoculated in orange and apple juice (11°Brix) were also tested. A total of 484 strains were isolated from 48 brands, and the species A. acidocaldarius and A. acidoterrestris were the most found among all samples analyzed. In some samples from Argentina, the species A. vulcanalis and A. mali were also identified. The incidence of these two main species of Alicyclobacillus in this study was mainly in products from pear (n = 108; 22.3 %), peach (n = 99; 20.5 %), apple (n = 86; 17.8 %), and tomato (n = 63; 13 %). The results indicated that from the total isolates from Argentina (n = 414), Brazil (n = 54) and Italy (n = 16) were able to produce guaiacol: 107 (25.8 %), 33 (61.1 %) and 13 (81.2 %) isolates from each country, respectively. The PCA score plot indicated that the Argentina and Brazil isolates correlate with higher production of guaiacol and 2,6-DCP/2,6-DBP, respectively. Heatmaps of cell survival after heat shock demonstrated that strains with different levels of guaiacol production present different resistances according to spoilage ability. None of the Alicyclobacillus isolates survived heat shocks at 120 °C for 3 min. This work provides insights into the incidence, spoilage potential, and thermal shock resistance of Alicyclobacillus strains isolated from fruit-based products.
Assuntos
Alicyclobacillus , Sucos de Frutas e Vegetais , Frutas , Cromatografia Gasosa-Espectrometria de Massas , Guaiacol , Esporos Bacterianos , Alicyclobacillus/isolamento & purificação , Alicyclobacillus/genética , Alicyclobacillus/classificação , Alicyclobacillus/crescimento & desenvolvimento , Sucos de Frutas e Vegetais/microbiologia , Guaiacol/análogos & derivados , Guaiacol/metabolismo , Guaiacol/farmacologia , Frutas/microbiologia , Esporos Bacterianos/crescimento & desenvolvimento , Esporos Bacterianos/isolamento & purificação , Microbiologia de Alimentos , Contaminação de Alimentos/análise , Brasil , Microextração em Fase Sólida , Argentina , Malus/microbiologia , Itália , Temperatura Alta , Citrus sinensis/microbiologiaRESUMO
Nitroimidazole compounds are well-known bioactive substances, and the structural activity relationship has been reported whereby the position of the nitro group within the imidazole ring has a large influence on the activity. This study focuses on synthesising new trypanocidal agents from the hybridisation of metronidazole with different natural phenols (eugenol, dihydroeugenol and guaiacol). Two different coupling methodologies have been explored in order to analyse the influence of the connector on bioactivity: i) classic direct esterification (AD compounds) and ii) "click" chemistry using a triazole connector (AC compounds). The in vitro trypanocidal tests show good results for both AC and AD hybrid compounds against both epimastigote and trypomastigote forms of T. cruzi. In silico studies showed positive data for most of the synthesised compounds and, in general present low toxicological risks. The AC compounds present lower ClogP (lipophilicity) values than those found for the AD series and higher TPSA (topological polar surface area) values, suggesting lower lipophilicity may be related to the presence of the triazole connector. The AD series compounds have higher Drug Score values than the AC series derivatives, suggesting better general properties for a pharmacological action.
Assuntos
Doença de Chagas , Tripanossomicidas , Trypanosoma cruzi , Humanos , Doença de Chagas/tratamento farmacológico , Eugenol , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Relação Estrutura-Atividade , Triazóis/uso terapêutico , Tripanossomicidas/química , Guaiacol/síntese química , Guaiacol/química , Guaiacol/farmacologiaRESUMO
Thirty-three meso-dihydroguaiaretic acid (meso-DGA) derivatives bearing esters, ethers, and amino-ethers were synthesized. All derivatives were tested against twelve drug-resistant clinical isolates of Gram-positive and Gram-negative bacteria, including sensitive (H37Rv) and multidrug-resistant Mycobacterium tuberculosis strains. Among the tested compounds, four esters (7, 11, 13, and 17), one ether (23), and three amino-ethers (30, 31, and 33) exhibited moderate activity against methicillin-resistant Staphylococcus aureus, whereas 30 and 31 showed better results than levofloxacin against vancomycin-resistant Enterococcus faecium. Additionally, nineteen meso-DGA derivatives displayed moderate to potent activity against M. tuberculosis H37Rv with minimum inhibitory concentration (MIC) values ranging from 3.125 to 50µg/mL. Seven meso-DGA derivatives bearing amino-ethers (26-31 and 33) exhibited the lowest MICs against M. tuberculosis H37Rv and G122 strains, with 31 being as potent as ethambutol (MICs of 3.125 and 6.25µg/mL). The presence of positively charged group precursors possessing steric and hydrophobic features (e.g. N-ethylpiperidine moieties in meso-31) resulted essential to significantly increase the antimycobacterial properties of parent meso-DGA as supported by the R-group pharmacophoric and field-based QSAR analyses. To investigate the safety profile of the antimycobacterial compounds, cytotoxicity on Vero cells was determined. The amino-ether 31 exhibited a selectivity index value of 23, which indicate it was more toxic to M. tuberculosis than to mammalian cells. Therefore, 31 can be considered as a promising antitubercular agent for further studies.
Assuntos
Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Guaiacol/análogos & derivados , Lignanas/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Guaiacol/síntese química , Guaiacol/química , Guaiacol/farmacologia , Lignanas/síntese química , Lignanas/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Quantitativa Estrutura-Atividade , Células VeroRESUMO
Breast cancer is a complex and multifactorial disease. Tumors have a heterogeneous microenvironment, which have multiple interactions with other cell types, greatly influencing the behavior of tumor cells and response to therapy. The 3D culture mimics the microenvironment better found in vivo and is more appropriated than the traditional 2D culture made from plastic to test the cellular response to drugs. To investigate the effects of [10]-gingerol on breast tumor cells, we used physiologically relevant three-dimensional (3D) cultures of malignant and non-malignant human breast cells grown in laminin-rich extracellular matrix gels (lr-ECM). Our results showed selective cytotoxicity of [10]-gingerol against the malignant T4-2 breast cancer cell line compared to non-malignant S1 cells. The compound reverted the malignant phenotype of the cancer cells, downregulating the expression of epidermal growth factor receptor (EGFR) and ß1-integrin. Moreover, [10]-gingerol induced apoptosis in this cell line. These results suggest that [10]-gingerol may be an effective compound to use as adjuvant therapy in breast cancer treatment. J. Cell. Biochem. 118: 2693-2699, 2017. © 2017 Wiley Periodicals, Inc.
Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Álcoois Graxos/farmacologia , Guaiacol/análogos & derivados , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Receptores ErbB/biossíntese , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Guaiacol/farmacologia , Humanos , Integrina beta1/biossíntese , Camundongos Nus , Proteínas de Neoplasias/biossínteseRESUMO
Cuprous oxide is the most commonly used biocide in antifouling paints. However, copper has harmful effects not only on the fouling community but also on non-target species. In the current study, we investigated the use of thymol, eugenol and guaiacol in this role combined with small quantities of copper. Phenolic compounds were tested for anti-settlement activity against cyprid larvae of the barnacle Balanus amphitrite and for their toxicity to nauplius larvae. Thymol, eugenol and guaiacol were active for anti-settlement but guaiacol had the disadvantage of being toxic to nauplius larvae. However, all of them showed therapeutic ratio>1. Antifouling paints with thymol (low copper content/thymol, LCP/T), eugenol (low copper content/eugenol, LCP/E) and guaiacol (low copper content/guaiacol, LCP/G) combined with small copper content were formulated for field trials. After 12 months exposure in the sea, statistical analysis revealed that LCP/T and LCP/E paints were the most effective combinations and had similar performances to control paints with high copper content (traditional cuprous oxide based paints). In contrast, LCP/G paint was only partially effective in preventing and inhibiting biofouling and was colonized by some hard and soft foulers. However, this antifouling paint was effective against calcareous tubeworm Hydroides elegans. In the light of various potential applications, thymol, eugenol and guaiacol have thus to be considered in future antifouling formulations.
Assuntos
Incrustação Biológica/prevenção & controle , Desinfetantes/farmacologia , Eugenol/farmacologia , Guaiacol/farmacologia , Thoracica/efeitos dos fármacos , Timol/farmacologia , Animais , Cobre/farmacologia , Larva/efeitos dos fármacos , Pintura/análise , Água do Mar , Thoracica/crescimento & desenvolvimentoRESUMO
Zingerone (1) and both chiral forms of zingerol (2) were obtained from dehydrozingerone (3) by biotransformation with filamentous fungi. The bioconversion of 3 with A. fumigatus, G. candidum or R. oryzae allowed the production of 1 as the sole product at 8 h and in 81%-90% at 72 h. In turn, A. flavus, A. niger, C. echinulata, M. circinelloides and P. citrinum produced 1 at 8 h, but at 72 h alcohol 2 was obtained as the major product (74%-99%). Among them, A. niger and M. circinelloides led to the anti-Prelog zingerol (R)-2 in only one step with high conversion rates and ee. Instead, C. echinulata and P. citrinum allowed to obtain (S)-2 in only one step, with high conversion rates and ee. Both chiral forms of 2 were tested for antifungal properties against a panel of clinically important fungi, showing that (R)-, but not (S)-2 possessed antifungal activity.
Assuntos
Antifúngicos/farmacologia , Biocatálise/efeitos dos fármacos , Aromatizantes/metabolismo , Fungos/metabolismo , Guaiacol/análogos & derivados , Biotransformação/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Ésteres/química , Aromatizantes/química , Aromatizantes/farmacologia , Fungos/efeitos dos fármacos , Guaiacol/química , Guaiacol/metabolismo , Guaiacol/farmacologia , Testes de Sensibilidade Microbiana , Espectroscopia de Prótons por Ressonância Magnética , Estereoisomerismo , Fatores de TempoRESUMO
The isolation and characterization of the lignan meso-dihydroguaiaretic acid (MDGA) from Larrea tridentata and its activity against Mycobacterial tuberculosis has been demonstrated, but no information regarding its mechanism of action has been documented. Therefore, in this study we carry out the gene expression from total RNA obtained from M. tuberculosis H37Rv treated with MDGA using microarray technology, which was validated by quantitative real time polymerase chain reaction. Results showed that the alpha subunit of coenzyme A transferase of M. tuberculosis H37Rv is present in both geraniol and 1-and 2-methylnaphthalene degradation pathways, which are targeted by MDGA. This assumption was supported by molecular docking which showed stable interaction between MDGA with the active site of the enzyme. We propose that inhibition of coenzyme A transferase of M. tuberculosis H37Rv results in the accumulation of geraniol and 1-and 2-methylnaphtalene inside bacteria, causing membrane destabilization and death of the pathogen. The natural product MDGA is thus an attractive template to develop new anti-tuberculosis drugs, because its target is different from those of known anti-tubercular agents.
Assuntos
Antituberculosos/farmacologia , Guaiacol/análogos & derivados , Lignanas/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Antituberculosos/química , Sítios de Ligação , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Genes Bacterianos , Guaiacol/química , Guaiacol/farmacologia , Lignanas/química , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/crescimento & desenvolvimento , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genéticaRESUMO
This paper describes a new method for the preparation of sodium 4-[5-(4-hydroxy-3-methoxyphenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate, DM-1, and 3-oxo-penta-1,4-dienyl-bis (2-methoxy-phenolate), DM-2. The aim of this work was to evaluate the antitumor effects of DM-1 in adjuvant chemotherapy for breast cancer treatment. Mice bearing mammary adenocarcinomas (Ehrlich ascites tumors) were treated with paclitaxel alone, DM-1 alone, and paclitaxel + DM-1. Tumor samples were used to perform cytological analysis by the Papanicolaou method and apoptosis analysis by annexin V and phosphorylated caspase 3. The paclitaxel + DM-1 group had decreased tumor areas and tumor volumes, and the frequency of metastasis was significantly reduced. This caused a decrease in cachexia, which is usually caused by the tumor. Furthermore, treatment with paclitaxel + DM-1 and DM-1 alone increased the occurrence of apoptosis up to 40% in tumor cells, which is 35% more than in the group treated with paclitaxel alone. This cell death was mainly caused through phosphorylated caspase 3 (11% increase in paclitaxel + DM-1 compared to the paclitaxel group), as confirmed by reduced malignancy criteria in the ascitic fluid. DM-1 emerges as a potential treatment for breast cancer and may act as an adjuvant in chemotherapy, enhancing antitumor drug activity with reduced side effects.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Guaiacol/análogos & derivados , Cetonas/uso terapêutico , Neoplasias Mamárias Experimentais/tratamento farmacológico , Adenocarcinoma/mortalidade , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Feminino , Guaiacol/administração & dosagem , Guaiacol/farmacologia , Guaiacol/uso terapêutico , Cetonas/administração & dosagem , Cetonas/farmacologia , Neoplasias Mamárias Experimentais/mortalidade , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Paclitaxel/administração & dosagem , Análise de Sobrevida , Carga Tumoral/efeitos dos fármacosRESUMO
Apocynin, a methoxy-substituted catechol (4-hydroxy-3-methoxyacetophenone), originally extracted from the roots of Picrorhiza kurroa, has been extensively used as a non-toxic inhibitor of the multienzymatic complex NADPH oxidase. We discovered that the analogous methoxy-substituted catechol, 4-Fluoro-2-methoxyphenol (F-apocynin), in which the acetyl group present in apocynin was changed to a fluorine atom, was significantly more potent as an inhibitor of NADPH oxidase activity, myeloperoxidase (MPO) chlorinating activity and phagocytosis of microorganisms by neutrophils; it was also as potent as apocynin in inhibiting tumor necrosis factor-alpha (TNFα) release by peripheral blood mononuclear cells. We attribute the increased potency of F-apocynin to its increased lipophilicity, which could facilitate the passage of the drug through the cell membrane. The inhibition of MPO chlorination activity, phagocytosis and TNFα release shows that apocynin and F-apocynin actions are not restricted to reactive oxygen species inhibition, but further studies are needed to clarify if these mechanisms are related. Like apocynin, F-apocynin did not show cell toxicity, and is a strong candidate for use in the treatment of inflammatory diseases.
Assuntos
Acetofenonas/química , Guaiacol/análogos & derivados , Leucócitos/efeitos dos fármacos , Oxidantes/biossíntese , Fagocitose/efeitos dos fármacos , Acetofenonas/metabolismo , Acetofenonas/farmacologia , Acetofenonas/toxicidade , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/metabolismo , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/toxicidade , Candida albicans/fisiologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Guaiacol/química , Guaiacol/metabolismo , Guaiacol/farmacologia , Guaiacol/toxicidade , Humanos , Interações Hidrofóbicas e Hidrofílicas , Ácido Hipocloroso/metabolismo , Leucócitos/imunologia , Leucócitos/metabolismo , Leucócitos/microbiologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Peroxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/fisiologia , Superóxidos/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Oral administration of a CH(2)Cl(2)-MeOH (1:1) extract of Scaphyglottis livida produced dose-dependent antinociceptive and anti-inflammatory effects when tested in mice and rats using the hot-plate (150-600 mg/kg) and carrageenan-induced inflammation (150-600 mg/kg) models, respectively. Morphine (1.5-6 mg/kg, p.o.) and indomethacin (10-40 mg/kg, p.o.) were used as positive controls, respectively. Four compounds were isolated from the active extract of Scaphyglottis livida, namely 5alpha-lanosta-24,24-dimethyl-9(11),25-dien-3beta-ol (LDD), 24,24,dimethyl-9,19-cyclolanosta-9(11),25-dien-3-one (cyclobalanone), gigantol and 3,4'-dihydroxy-3',4,5-trimethoxybibenzyl (DTB). LDD and gigantol (25-100 mg/kg, p.o.) significantly increased the hot-plate latency in comparison to vehicle-treated mice and decreased carrageenan-induced inflammation in rats. The antinociception provoked by LDD and gigantol was partially blocked by naloxone (1mg/kg, i.p.). However, pretreatment with L-NAME (100 mg/kg, i.p.) and glibenclamide (10 mg/kg, i.p.) did not affect the antinociceptive response induced by LDD or gigantol suggesting that their pharmacological effect could be partially due to activation of opioid receptors. Moreover, a CH(2)Cl(2)-MeOH (1:1) extract of Maxillaria densa reduced acetic acid-induced abdominal writhes but was not able to produce antinociception in the hot-plate assay. Two compounds were isolated from the active extract of Maxillaria densa, namely fimbriol A and erianthridin. Both compounds partially reduced acetic acid-induced writhes. The results tend to support the popular use of this species in folk medicine for treatment of painful complaints.