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1.
Am J Infect Control ; 51(9): 1011-1016, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36736900

RESUMO

BACKGROUND: Adenoviruses belong to the stable nonenveloped viruses playing an important role in healthcare-associated infections mainly causing respiratory infections and epidemic keratoconjunctivitis. Hand disinfection with alcoholic preparations is therefore one of the most important measures to prevent such viral infections in hospitals and other medical settings. METHODS: The inactivation of adenovirus type 5 by ethanol, 1- and 2-propanol, and 2 commercially available hand disinfectants was examined at different concentrations, temperatures, and pH-values. RESULTS: For ethanol and 1-propanol the maximum virus-inactivating properties after 30 seconds exposure were found at a concentration of 60%-70% and 50%-60%, respectively, whereas with 2-propanol no activity was observed. The virucidal activity of all alcohols and the 2 hand disinfectants examined was increased when raising the temperature from 20°C to 25°C. By increasing the pH value to 9, a strong improvement of the activity of ethanol, 1-propanol and 1 hand disinfectant was observed, whereas pH lowering resulted in decrease of activity. CONCLUSIONS: These results demonstrate the importance of physical parameters in the inactivation of adenoviruses by alcohols and will help to improve measures to reduce adenovirus transmission in healthcare settings.


Assuntos
Adenovírus Humanos , Desinfetantes , Higienizadores de Mão , Humanos , Álcoois/farmacologia , Temperatura , 2-Propanol , 1-Propanol , Desinfetantes/farmacologia , Etanol/farmacologia , Concentração de Íons de Hidrogênio
2.
Int J Mol Sci ; 23(19)2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36232458

RESUMO

The chemical composition, investigated by gas chromatography-mass spectrometry, and antibacterial activity of lipophilic extractives of three varieties of Opuntia ficus-indica roots from Algeria are reported in this paper for the first time. The results obtained revealed a total of 55 compounds, including fatty acids, sterols, monoglycerides and long chain aliphatic alcohols that were identified and quantified. ß-Sitosterol was found as the major compound of the roots of the three varieties. Furthermore, considerable amounts of essential fatty acids (ω3, ω6, and ω9) such as oleic, linoleic, and linolenic acids were also identified. The green variety was the richest among the three studied varieties. The antibacterial activity, evaluated with disc diffusion method, revealed that lipophilic extracts were effective mainly against Gram-positive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) (19~23 mm). Gram-negative strains mainly Pseudomonas aeruginosa gave an inhibition zone of 18 mm, which is considered high antibacterial activity. The minimal inhibitory concentrations of the tested bacteria revealed interesting values against the majority of bacteria tested: 75-100 µg mL-1 for Bacillus sp., 250-350 µg/mL for the two Staphylococcus strains, 550-600 µg mL-1 for E. coli, and 750-950 µg mL-1 obtained with Pseudomonas sp. This study allows us to conclude that the lipophilic fractions of cactus roots possess interesting phytochemicals such as steroids, some fatty acids and long chain alcohols that acted as antibiotic-like compounds countering pathogenic strains.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Opuntia , Fitosteróis , Álcoois/farmacologia , Argélia , Antibacterianos/química , Antibacterianos/farmacologia , Escherichia coli , Ácidos Linolênicos/farmacologia , Testes de Sensibilidade Microbiana , Monoglicerídeos/farmacologia , Opuntia/química , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Fitosteróis/farmacologia , Extratos Vegetais/química
3.
Molecules ; 27(13)2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35807254

RESUMO

In vitro studies can help reveal the biochemical pathways underlying the origin of volatile indicators of numerous diseases. The key objective of this study is to identify the potential biomarkers of gastric cancer. For this purpose, the volatilomic signatures of two human gastric cancer cell lines, AGS (human gastric adenocarcinoma) and SNU-1 (human gastric carcinoma), and one normal gastric mucosa cell line (GES-1) were investigated. More specifically, gas chromatography mass spectrometry has been applied to pinpoint changes in cell metabolism triggered by cancer. In total, ten volatiles were found to be metabolized, and thirty-five were produced by cells under study. The volatiles consumed were mainly six aldehydes and two heterocyclics, whereas the volatiles released embraced twelve ketones, eight alcohols, six hydrocarbons, three esters, three ethers, and three aromatic compounds. The SNU-1 cell line was found to have significantly altered metabolism in comparison to normal GES-1 cells. This was manifested by the decreased production of alcohols and ketones and the upregulated emission of esters. The AGS cells exhibited the increased production of methyl ketones containing an odd number of carbons, namely 2-tridecanone, 2-pentadecanone, and 2-heptadecanone. This study provides evidence that the cancer state modifies the volatilome of human cells.


Assuntos
Neoplasias Gástricas , Compostos Orgânicos Voláteis , Álcoois/análise , Álcoois/farmacologia , Linhagem Celular , Ésteres/análise , Humanos , Cetonas/análise , Cetonas/farmacologia , Compostos Orgânicos Voláteis/análise
4.
J Med Chem ; 65(15): 10471-10480, 2022 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-35857416

RESUMO

The mechanism for the cutoff, an activity cliff at which long-chain alcohols lose their biological effects, has not been elucidated. Highly hydrophobic oleyl alcohol (C18:1) exists as a mixture of monomers and aggregated droplets in water. C18:1 did not inhibit the yeast growth but inhibited the growth of the slime mold without a cell wall. C18:1 exhibited toxicity to the yeast protoplast, which was enhanced by polyethylene glycol, a fusogen. Therefore, direct interactions of C18:1 with the membrane are crucial for the toxicity. The cutoff alcohols, C14 and C16, also exhibited strong toxicity obeying the Meyer-Overton correlation, in intact yeast cells whose membrane growth was suppressed in water. Taken together, the cutoff is avoidable by securing sufficient accumulation of the wall-permeable monomers in the membrane, which supports the lipid theory. It would be important to distinguish the effective drug structure localizing in the membrane and deal with the amount in the membrane.


Assuntos
Álcoois , Saccharomyces cerevisiae , Álcoois/farmacologia , Membrana Celular , Água
5.
Cells ; 11(12)2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35741057

RESUMO

Alcohols are a part of cellular metabolism, but their physiological roles are not well understood. We investigated the effects of short-chain alcohols on Daphnia pulex and model membranes mimicking the lipid composition of eukaryotic inner mitochondrial membranes. We also studied the synergistic effects of alcohols with the bee venom membrane-active peptide, melittin, which is structurally similar to endogenous membrane-active peptides. The alcohols, from ethanol to octanol, gradually decreased the heart rate and the mitochondrial ATP synthesis of daphnia; in contrast, in combination with melittin, which exerted no sizeable effect, they gradually increased both the heart rate and the ATP synthesis. Lipid packing and the order parameter of oriented films, monitored by EPR spectroscopy of the spin-labeled probe 5-doxylstrearic acid, revealed gradual alcohol-assisted bilayer to non-bilayer transitions in the presence of melittin; further, while the alcohols decreased, in combination with melittin they increased the order parameter of the film, which is attributed to the alcohol-facilitated association of melittin with the membrane. A 1H-NMR spectroscopy of the liposomes confirmed the enhanced induction of a non-bilayer lipid phase that formed around the melittin, without the permeabilization of the liposomal membrane. Our data suggest that short-chain alcohols, in combination with endogenous peptides, regulate protein functions via modulating the lipid polymorphism of membranes.


Assuntos
Venenos de Abelha , Meliteno , Trifosfato de Adenosina , Álcoois/farmacologia , Venenos de Abelha/farmacologia , Lipídeos , Lipossomos , Meliteno/química , Meliteno/metabolismo , Meliteno/farmacologia
6.
J Hosp Infect ; 127: 26-33, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35690267

RESUMO

BACKGROUND: Since the advent of the COVID-19 pandemic, alcohol-based hand sanitizer dispensers (HSDs) have been installed in most public and clinical settings for hygiene purposes and convenient application. AIM: To determine whether sanitizer-tolerant bacterial pathogens can colonize HSDs, spreading diseases and antibiotic resistance. METHODS: Sampling was conducted from operational automatic HSDs, specifically the dispensing nozzle in direct contact with sanitizer. Culture-dependent cultivation of bacteria and MALDI-TOF were employed to assess microbiological contamination. Bacterial isolates were selected for rapid killing and biofilm eradication assays with alcohol treatment. Antibiotic minimum inhibitory concentration assays were performed according to the Clinical and Laboratory Standards Institute guidelines. Virulence potential of bacterial isolates was evaluated in the Caenorhadbitis elegans infection model. FINDINGS: Nearly 50% of HSDs from 52 locations, including clinical settings, food industry, and public spaces, contain microbial contamination at 103-106 bacteria/mL. Bacterial identification revealed Bacillus cereus as the most frequent pathogen (29%), while Enterobacter cloacae was the only Gram-negative bacterial pathogen (2%). Selecting B. cereus and E. cloacae isolates for further evaluation, these isolates and associated biofilms were found to be tolerant to alcohol with survival up to 70%. They possessed resistance to various antibiotic classes, with higher virulence than laboratory strains in the C. elegans infection model. CONCLUSION: HSDs serve as potential breeding grounds for dissemination of pathogens and antibiotic resistance across unaware users. Proper HSD maintenance will ensure protection of public health and sustainable use of sanitizing alcohols, to prevent emergence of alcohol-resistant pathogens.


Assuntos
COVID-19 , Higienizadores de Mão , Álcoois/farmacologia , Animais , Antibacterianos/farmacologia , Bactérias , Caenorhabditis elegans , Farmacorresistência Bacteriana , Higienizadores de Mão/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Pandemias , Prevalência
7.
FEMS Microbiol Ecol ; 98(4)2022 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-35298615

RESUMO

Within the oral cavity, the ability of Candida species to adhere and form biofilms is well-recognized, especially when Candida albicans is considered. Lately, a knowledge gap has been identified regarding dual-species communication of Candida isolates, as a way to increase virulence, with evidences being collected to support the existence of interactions between C. albicans and Candida parapsilosis. The present work evaluated the synergistic effect of the two Candida species, and explored chemical interactions between cells, evaluating secreted extracellular alcohols and their relation with yeasts' growth and matrix composition. A total of four clinical strains of C. albicans and C. parapsilosis species, isolated from single infections of different patients or from co-infections of a same patient, were tested. It was found that dual-species biofilms negatively impacted the growth of C. parapsilosis and their biofilm matrix, in comparison with mono-species biofilms, and had minor effects on the biofilm biomass. Alcohol secretion revealed to be species- and strain-dependent. However, some dual-species cultures produced much higher amounts of some alcohols (E-nerolidol and E, E-Farnesol) than the respective single cultures, which proves the existence of a synergy between species. These results show evidence that interactions between Candida species affect the biofilm matrix, which is a key element of oral biofilms.


Assuntos
Candida albicans , Candida parapsilosis , Álcoois/metabolismo , Álcoois/farmacologia , Biofilmes , Candida , Candida parapsilosis/metabolismo , Humanos , Metaboloma
8.
Arch Pharm (Weinheim) ; 355(5): e2100443, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35137966

RESUMO

A new protocol for the N-alkylation of amines with alcohols for the synthesis of tertiary amines in the presence of MnCl2 as a catalyst, under microwave conditions, is described. The advantages of this protocol include stable reaction profiles, a wide substrate variety, excellent yields, low cost, high yields, and easy workup conditions. The anticancer efficacy of all the synthesized compounds was tested in vitro against various cancer cell lines, such as MCF-7, MDA-MB-231 (human breast), HT-29, HCT 116 (colon cancer), A549 (human lung carcinoma), and Vero cells. Among the screened compounds, 3e, 3h, and 3i demonstrated potent anticancer activity, with compound 3h surpassing the reference drug cisplatin against A549, MCF7, MDA-MB-231, and HCT116 cancer cells. The introduction of an electron-withdrawing group on the phenyl ring resulted in increased anticancer activity. The most potent compounds, 3e, 3h, and 3i, were tested against VEGFR-2, HER2, and EGFR in multikinase inhibition assays, with compounds 3h and 3i showing improved potency against the HER2 kinase. The compounds formed two H-bonds with amino acids, indicating that they had a high affinity for the target HER2 kinase (PDB ID: 3RCD), according to the docking analysis. The absorption, distribution, metabolism, excretion, and toxicity properties of the optimized analogs were also assessed in vitro, enabling the discovery of promising anticancer agents. Finally, the B3LYP level was used to measure density functional theory geometry optimization and the related quantum parameters for the active compounds.


Assuntos
Aminas , Antineoplásicos , Álcoois/farmacologia , Alquilação , Aminas/farmacologia , Animais , Catálise , Linhagem Celular Tumoral , Proliferação de Células , Chlorocebus aethiops , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Micro-Ondas , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Células Vero
9.
Eur J Med Chem ; 227: 113953, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34731760

RESUMO

As epigenetic readers, bromodomain and extra-terminal domain (BET) family proteins bind to acetylated-lysine residues in histones and recruit protein complexes to promote transcription initiation and elongation. Inhibition of BET bromodomains by small molecule inhibitors has emerged as a promising therapeutic strategy for cancer. Herein, we describe our efforts toward the discovery of a novel series of 1-(5-(1H-benzo[d]imidazole-2-yl)-2,4-dimethyl-1H-pyrrol-3-yl)ethan-1-one derivatives as BET inhibitors. Intensive structural modifications led to the identification of compound 35f as the most active inhibitor of BET BRD4 with selectivity against BET family proteins. Further biological studies revealed that compound 35f can arrest the cell cycle in G0/G1 phase and induce apoptosis via decreasing the expression of c-Myc and other proteins related to cell cycle and apoptosis. More importantly, compound 35f showed favorable pharmacokinetic properties and antitumor efficacy in MV4-11 mouse xenograft model with acceptable tolerability. These results indicated that BET inhibitors could be potentially used to treat hematologic malignancies and some solid tumors.


Assuntos
Álcoois/farmacologia , Antineoplásicos/farmacologia , Benzimidazóis/farmacologia , Proteínas de Ciclo Celular/antagonistas & inibidores , Descoberta de Drogas , Pirróis/farmacologia , Fatores de Transcrição/antagonistas & inibidores , Álcoois/síntese química , Álcoois/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Benzimidazóis/síntese química , Benzimidazóis/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Pirróis/síntese química , Pirróis/química , Relação Estrutura-Atividade , Fatores de Transcrição/metabolismo
10.
Biomed Res Int ; 2021: 5536030, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395619

RESUMO

Argania spinosa (L.) plays an important role in the Moroccan agroeconomy, providing both employment and export revenue. Argan oil production generates different by-products with functionalities that are not yet investigated, in particular, the shell fruit. The present study aims, for the first time, at evaluating the acute and subacute toxicity, anti-inflammatory, and antioxidant effects of argan fruit shell ethanol extract (AFSEE). The LD50 of AFSEE was determined to be greater than the 5000 mg/kg body weight of mice. No significant variation in the body and organ weights was observed after 28 days of AFSEE treatment compared to that of the control group. Biochemical parameters and histopathological examination revealed no toxic effects of AFSEE. The AFSEE produced a significant inhibition of xylene-induced ear edema in mice. AFSEE reduced significantly the paw edema in mice after carrageenan injection. The chemical characterization showed that AFSEE contains a high level of total phenol content, flavonoids, condensed tannins, and flavanols. The obtained IC50 of DPPH, ABTS, reducing power, and ß-carotene demonstrates that AFSEE has a potential antioxidant effect. The results indicate that AFSEE was safe and nontoxic to mice even at higher doses. Furthermore, the present findings demonstrate that AFSEE has potential anti-inflammatory and antioxidant activities.


Assuntos
Álcoois/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Edema/tratamento farmacológico , Sapotaceae/química , Xilenos/toxicidade , Álcoois/química , Álcoois/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Dose Letal Mediana , Masculino , Camundongos , Marrocos , Extratos Vegetais/química
11.
Int J Mol Sci ; 22(11)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199599

RESUMO

Orphan nuclear receptor estrogen-related receptor γ (ERRγ) is an important transcription factor modulating gene transcription involved in endocrine control of liver metabolism. Transferrin receptor 2 (TFR2), a carrier protein for transferrin, is involved in hepatic iron overload in alcoholic liver disease (ALD). However, TFR2 gene transcriptional regulation in hepatocytes remains largely unknown. In this study, we described a detailed molecular mechanism of hepatic TFR2 gene expression involving ERRγ in response to an endocannabinoid 2-arachidonoylglycerol (2-AG). Treatment with 2-AG and arachidonyl-2'-chloroethylamide, a selective cannabinoid receptor type 1 (CB1) receptor agonist, increased ERRγ and TFR2 expression in hepatocytes. Overexpression of ERRγ was sufficient to induce TFR2 expression in both human and mouse hepatocytes. In addition, ERRγ knockdown significantly decreased 2-AG or alcohol-mediated TFR2 gene expression in cultured hepatocytes and mouse livers. Finally, deletion and mutation analysis of the TFR2 gene promoter demonstrated that ERRγ directly modulated TFR2 gene transcription via binding to an ERR-response element. This was further confirmed by chromatin immunoprecipitation assay. Taken together, these results reveal a previously unrecognized role of ERRγ in the transcriptional regulation of TFR2 gene expression in response to alcohol.


Assuntos
Hepatopatias Alcoólicas/genética , Fígado/efeitos dos fármacos , Receptor CB1 de Canabinoide/genética , Receptores de Estrogênio/genética , Receptores da Transferrina/genética , Álcoois/farmacologia , Animais , Ácidos Araquidônicos/farmacologia , Endocanabinoides/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glicerídeos/farmacologia , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Humanos , Ferro/metabolismo , Fígado/metabolismo , Fígado/patologia , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/patologia , Camundongos , Regiões Promotoras Genéticas , Receptor CB1 de Canabinoide/agonistas , Deleção de Sequência/genética , Transferrina/genética , Transferrina/metabolismo
12.
Vet Parasitol ; 296: 109496, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34147018

RESUMO

Gastrointestinal nematodes (GIN) infections are a serious problem in livestock production due to the great economic losses they cause. Their control is increasingly difficult because of the rapid development of drug resistance and the limited number of available drugs. Therefore, this study evaluated 18 aminoalcohol and 16 diamine derivatives against eggs, first and third stage larvae from a susceptible and a resistant isolate of Teladorsagia circumcincta collected from sheep. The effectiveness of the in vitro anthelmintic activity of the compounds was evaluated using three different procedures: Egg Hatch Test (EHT), Larval Mortality Test (LMT) and Larval Migration Inhibition Test (LMIT). Those compounds with activities higher than 90 % in the initial screening at 50 µM were selected to determine their half maximal effective concentration (EC50). In parallel, cytotoxicity assays were conducted on Caco2 and HepG2 cell lines to calculate Selectivity Indexes (SI) for each compound. The diamine 30 presented the best results in preventing egg hatching, displaying the lowest EC50 value (1.01 ±â€¯0.04 µM) of all compounds tested and the highest SI (21.21 vs. Caco-2 cells). For the LMIT, the diamine 34 showed the highest efficacy, with EC50 values of 2.67 ±â€¯0.08 and 3.02 ±â€¯0.09 µM on the susceptible and resistant isolate of the parasite, respectively.


Assuntos
Álcoois , Anti-Helmínticos , Diaminas , Nematoides , Doenças dos Ovinos , Álcoois/farmacologia , Álcoois/uso terapêutico , Animais , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Células CACO-2 , Diaminas/farmacologia , Diaminas/uso terapêutico , Resistência a Medicamentos/efeitos dos fármacos , Fezes , Humanos , Óvulo/efeitos dos fármacos , Ovinos , Doenças dos Ovinos/tratamento farmacológico
13.
Arch Pharm Res ; 44(5): 514-524, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33929687

RESUMO

Ginkgo biloba (Ginkgoaceae), commonly known as "ginkgo", is called a living fossil, and it has been cultivated early in human history for various uses in traditional medicine and as a source of food. As part of ongoing research to explore the chemical diversity and biologically active compounds from natural resources, two new coumaric acid-aliphatic alcohol hybrids, ginkwanghols A (1) and B (2) were isolated from the leaves of G. biloba. The coumaric acid-aliphatic alcohol hybrids of natural products have rarely been reported. The structures of the new compounds were determined by extensive NMR spectroscopic analysis, HRESI-MS, and quantum chemical ECD calculations, and by comparing the experimental HRESI-MS/MS spectrum of chemically transformed compound 1a with the predicted HRESI-MS/MS spectra proposed from CFM-ID 3.0, a software tool for MS/MS spectral prediction and MS-based compound identification. Ginkwanghols A (1) and B (2) increased alkaline phosphatase (ALP) production in C3H10T1/2, a mouse mesenchymal stem cell line, in a dose-dependent manner. In addition, ginkwanghols A and B mediated the promotion of osteogenic differentiation as indicated by the induction of the mRNA expression of the osteogenic markers ALP and osteopontin (OPN).


Assuntos
Álcoois/farmacologia , Ácidos Cumáricos/farmacologia , Ginkgo biloba/química , Folhas de Planta/química , Álcoois/química , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Ácidos Cumáricos/química , Camundongos , Estrutura Molecular , Osteogênese/efeitos dos fármacos
14.
J Biosci Bioeng ; 131(5): 491-500, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33610455

RESUMO

Cyanobacteria hold promise as cell factories for the photoautotrophic conversion of carbon dioxide to useful chemicals. For the eventual commercial viability of such processes, cyanobacteria need to be engineered for (i) efficient channeling of carbon flux toward the product of interest and (ii) improved product tolerance, the latter being the focus of this study. We chose the recently reported, fast-growing, high light and CO2 tolerant cyanobacterium Synechococcus elongatus PCC 11801 for adaptive laboratory evolution. In two parallel experiments that lasted over 8400 h of culturing and 100 serial passages, S. elongatus PCC 11801 was evolved to tolerate 5 g/L n-butanol or 30 g/L 2,3-butanediol representing a 100% improvement in concentrations tolerated. The evolved strains retained alcohol tolerance even after being passaged several times without the alcohol stress suggesting that the changes were permanent. Whole genome sequencing of the n-butanol evolved strains revealed mutations in a number of stress responsive genes encoding translation initiation factors, RpoB and an ABC transporter. In 2,3-butanediol evolved strains, genes for ClpC, a different ABC transporter, glyceraldehyde-3-phosphate dehydrogenase and phosphoribulokinase were found to be mutated. Furthermore, the evolved strains showed significant improvement in tolerance toward several other alcohols. Notably, the n-butanol evolved strain could tolerate up to 32 g/L ethanol, thereby making it a promising host for photosynthetic production of biofuels via metabolic engineering.


Assuntos
Evolução Molecular Direcionada , Solventes/farmacologia , Synechococcus/efeitos dos fármacos , Synechococcus/genética , Álcoois/farmacologia , Biocombustíveis , Dióxido de Carbono/metabolismo , Fotossíntese/efeitos dos fármacos , Synechococcus/metabolismo
15.
Med Chem ; 17(8): 926-936, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32807064

RESUMO

BACKGROUND: Coumarins are naturally occurring biologically active heterocyclic molecules endowed with a wide range of biological properties, including antibacterial, antifungal, and antitumor activities. OBJECTIVE: The present work was aimed to synthesize new coumarin-containing compounds and to investigate their cytotoxic activity. METHODS: Coumarin peptide and coumarin amino alcohols were prepared by treating epoxidecontaining coumarin derivatives with suitable aromatic amines and peptides in trifluoroethanol as a solvent at 50°C. These derivatives were evaluated for their cytotoxic activity on three different cell lines: HeLa, MDA-MB-231 and L-132. Cell viability was determined by MTT (3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. RESULTS: A new protocol was developed for the synthesis of thirteen novel coumarin peptide and coumarin amino alcohol derivatives. Among the tested compounds, three derivatives showed significant activity against all the tested cell lines. Docking studies indicated favorable interactions of the disubstituted peptide coumarin derivatives with the Asp 351 and Thr 347 amino acids at the active site of the human estrogen receptor. CONCLUSIONS: The results suggest that the synthesized compounds may be promising candidates in the research of new antitumor compounds.


Assuntos
Álcoois/síntese química , Álcoois/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Cumarínicos/química , Peptídeos/química , Álcoois/química , Antineoplásicos/química , Linhagem Celular Tumoral , Técnicas de Química Sintética , Humanos
16.
Int J Biol Macromol ; 166: 1131-1140, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33161081

RESUMO

Phospholipase D (PLD) is a ubiquitous enzyme that cleaves the distal phosphoester bond of phospholipids generating phosphatidic acid (PA). In plants, PA is involved in numerous cell responses triggered by stress. Similarly, in mammals, PA is also a second messenger involved in tumorigenesis. PLD is nowadays considered as a therapeutic target and blocking its activity with specific inhibitors constitutes a promising strategy to treat cancers. Starting from already described PLD inhibitors, this study aims to investigate the effect of their structural modifications on the enzyme's activity, as well as identifying new potent inhibitors of eukaryotic PLDs. Being able to purify the plant PLD from Vigna unguiculata (VuPLD), we obtained a SAXS model of its structure. We then used a fluorescence-based test suitable for high-throughput screening to review the effect of eukaryotic PLD inhibitors described in the literature. In this regard, we found that only few molecules were in fact able to inhibit VuPLD and we confirmed that vanadate is the most potent of all with an IC50 around 58 µM. Moreover, the small-scale screening of a chemical library of 3120 compounds allowed us to optimize the different screening's steps and paved the way towards the discovery of new potent inhibitors.


Assuntos
Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/análise , Inibidores Enzimáticos/farmacologia , Fosfolipase D/antagonistas & inibidores , Álcoois/farmacologia , Ensaios de Triagem em Larga Escala , Humanos , Hidrólise , Fosfolipase D/metabolismo , Sais/farmacologia , Espalhamento a Baixo Ângulo , Vanadatos/farmacologia , Vigna/enzimologia , Difração de Raios X
17.
Infect Dis Health ; 26(1): 63-66, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33012695

RESUMO

BACKGROUND: Non-therapeutic interventions such as practicing good hand hygiene continue to be the mainstay of protection from SARS-CoV-2 and other emerging respiratory viruses. METHODS: We have evaluated a range of commercially available personal care products including soaps, handwash liquids and alcohol-based hand sanitizers for antiviral efficacy against a clinical isolate of SARS-CoV-2 using internationally accepted standardized protocols at user-relevant contact time-points and product dilutions. RESULTS: All the tested products resulted in 3 to 4 log reduction of SARS-CoV-2 titer. CONCLUSION: Our data re-affirms recommendations by global public health authorities that proper hand hygiene can reduce SARS-CoV-2 viral load significantly which should likely limit spread of the contagion.


Assuntos
Antivirais/farmacologia , COVID-19/prevenção & controle , Desinfecção das Mãos/métodos , SARS-CoV-2/efeitos dos fármacos , Inativação de Vírus/efeitos dos fármacos , Álcoois/farmacologia , Antivirais/classificação , Higienizadores de Mão/farmacologia , Humanos , Sabões/farmacologia
18.
Nat Microbiol ; 6(1): 103-111, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33106672

RESUMO

Nosocomial acquisition and transmission of vancomycin-resistant Enterococcus faecium (VREfm) is the driver for E. faecium carriage in hospitalized patients, which, in turn, is a risk factor for invasive infection in immunocompromised patients. In the present study, we provide a comprehensive picture of E. faecium transmission in an entire sampled patient population using a sequence-driven approach. We prospectively identified and followed 149 haematology patients admitted to a hospital in England for 6 months. Patient stools (n = 376) and environmental swabs (n = 922) were taken at intervals and cultured for E. faecium. We sequenced 1,560 isolates (1,001 stool, 559 environment) and focused our genomic analyses on 1,477 isolates (95%) in the hospital-adapted clade A1. Of 101 patients who provided two or more stool samples, 40 (40%) developed E. faecium carriage after admission based on culture, compared with 64 patients (63%) based on genomic analysis (73% VREfm). Half of 922 environmental swabs (447, 48%) were positive for VREfm. Network analysis showed that, of 111 patients positive for the A1 clade, 67 had strong epidemiological and genomic links with at least one other patient and/or their direct environment, supporting nosocomial transmission. Six patients (3.4%) developed an invasive E. faecium infection from their own gut-colonizing strain, which was preceded by nosocomial acquisition of the infecting isolate in half of these. Two informatics approaches (subtype categorization to define phylogenetic clusters and the development of an SNP cut-off for transmission) were central to our analyses, both of which will inform the future translation of E. faecium sequencing into routine outbreak detection and investigation. In conclusion, we showed that carriage and environmental contamination by the hospital-adapted E. faecium lineage were hyperendemic in our study population and that improved infection control measures will be needed to reduce hospital acquisition rates.


Assuntos
Infecção Hospitalar/epidemiologia , Enterococcus faecium/genética , Infecções por Bactérias Gram-Positivas/transmissão , Controle de Infecções/métodos , Enterococos Resistentes à Vancomicina/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Álcoois/farmacologia , Antibacterianos/farmacologia , Clorexidina/farmacologia , Infecção Hospitalar/transmissão , Surtos de Doenças , Desinfetantes/farmacologia , Enterococcus faecium/isolamento & purificação , Genoma Bacteriano/genética , Infecções por Bactérias Gram-Positivas/patologia , Humanos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Prospectivos , Vancomicina/farmacologia , Enterococos Resistentes à Vancomicina/isolamento & purificação , Sequenciamento Completo do Genoma , Adulto Jovem
19.
J Infect Dis ; 223(4): 714-718, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32623454

RESUMO

Tick-borne encephalitis virus (TBEV) is a single-stranded, positive-sense RNA virus in the family Flaviviridae that is endemic in parts of Europe and Asia and can cause meningitis or encephalitis. Due to the disease severity, TBEV requires handling under heightened biosafety measures. The establishment and validation of inactivation procedures is a prerequisite for downstream analyses and management of occupational exposure. Therefore, different procedures for TBEV inactivation were tested. Our results suggest that TBEV is susceptible to inactivation by heat, acidic pH, different concentrations of alcohol, formaldehyde, or detergents, and exposure to UV irradiation, which may depend on sample size and composition.


Assuntos
Vírus da Encefalite Transmitidos por Carrapatos/fisiologia , Inativação de Vírus , Células A549 , Álcoois/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Detergentes/farmacologia , Vírus da Encefalite Transmitidos por Carrapatos/efeitos dos fármacos , Formaldeído/farmacologia , Temperatura Alta , Humanos , Concentração de Íons de Hidrogênio , Polímeros/farmacologia , Raios Ultravioleta , Carga Viral/efeitos dos fármacos
20.
Epidemiol Infect ; 148: e229, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32988431

RESUMO

The pandemic due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged as a serious global public health issue. Since the start of the outbreak, the importance of hand-hygiene and respiratory protection to prevent the spread of the virus has been the prime focus for infection control. Health regulatory organisations have produced guidelines for the formulation of hand sanitisers to the manufacturing industries. This review summarises the studies on alcohol-based hand sanitisers and their disinfectant activity against SARS-CoV-2 and related viruses. The literature shows that the type and concentration of alcohol, formulation and nature of product, presence of excipients, applied volume, contact time and viral contamination load are critical factors that determine the effectiveness of hand sanitisers.


Assuntos
Álcoois/química , Betacoronavirus/efeitos dos fármacos , Higienizadores de Mão/química , Higienizadores de Mão/normas , Álcoois/farmacologia , Betacoronavirus/química , COVID-19 , Coronavirus/química , Coronavirus/efeitos dos fármacos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Contaminação de Medicamentos , Higienizadores de Mão/farmacologia , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , SARS-CoV-2
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