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1.
Dalton Trans ; 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34989381

RESUMO

We have synthesized and characterized three new ruthenium(II) diphosphine complexes containing an acylthiourea ligand, with the general formula [Ru(DPEPhos)(O,S)(bipy)]PF6, where DPEPhos = bis(2-(diphenylphosphino)phenyl)ether, bipy = 2,2'-bipyridine, and O,S = N,N-dimethyl-N'-(benzoyl)thiourea (1), N,N-dimethyl-N'-(furoyl)thiourea (2), and N,N-dimethyl-N'-(thiophenyl)thiourea (3), by several physicochemical techniques. We evaluated the ruthenium complexes for their cytotoxicity against two human cancer cell lines, A549 (lung) and MDA-MB-231 (breast), and two corresponding lines of non-cancer cells, MRC-5 (lung) and MCF-10A (breast). All the complexes are cytotoxic against the cancer cell lines; the IC50 values lie in the micromolar range (0.07-0.70 µM). Ruthenium complex 1 is more selective (7 times more active) toward lung cancer cells (A549) than toward non-cancer cells (MRC-5) and is 160 times more cytotoxic than cisplatin against A549 cells. Investigations of the mechanism of action of complex 1 in A549 cells demonstrated that it inhibits colony formation and promotes cell cycle arrest in the G1 phase and apoptotic cell death. DNA binding studies revealed that complexes 1-3 interact with the biomolecule via minor grooves. These complexes also interact with human serum albumin (HSA) and have affinity for site I by hydrophobic forces. Therefore, this new class of ruthenium complexes can act as cytotoxic agents, mainly for lung cancer treatment.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34748175

RESUMO

The year 2020 was atypical due to the pandemic caused by the SARS-CoV-2 virus (COVID-19), providing a unique opportunity to understand changes in air quality due to the reduction in urban activity. Therefore, the aim of the present study was to perform an integrated evaluation on the influence of the effects of the 2020 pandemic on air quality in the city of Fortaleza, investigating levels of PM2.5, PM10, NO2, NO, SO2, CO, and O3, corresponding health risks, as well as the influence of meteorological variables and urban activity. In all phases analyzed, significant reductions were found in NOx, NO, NO2, and CO. A considerable reduction in PM2.5 and PM10 was found in the early phases, with an increase in the later phases. These findings are explained by the nearly 50% reduction in vehicular traffic and the consequent reduction in fossil fuel emissions, mainly in the partial lockdown and total lockdown periods, as well as reductions in commercial (stores/shops) and industrial activities. The variation in O3 was initially non-significant, followed by a considerable increase in the last three phases analyzed; this increase was influenced by changes in temperature and the incidence of sunlight. SO2 concentrations increased in the period studied, demonstrating that the vehicular fleet, local commerce, and other activities are not the predominant sources of this compound. Estimated health risks were reduced by half during the lockdown period, especially for non-smokers, followed by a drastic increase in the last three phases. The planetary boundary layer was positively correlated with O3 and PM10 and negatively correlated with NOx, NO2, and NO, indicating its influence on the distribution of pollutants in the lower atmosphere and, consequently, air quality.

3.
Inorg Chem ; 60(18): 14174-14189, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34477373

RESUMO

Ruthenium(II) complexes (Ru1-Ru5), with the general formula [Ru(N-S)(dppe)2]PF6, bearing two 1,2-bis(diphenylphosphino)ethane (dppe) ligands and a series of mercapto ligands (N-S), have been developed. The combination of these ligands in the complexes endowed hydrophobic species with high cytotoxic activity against five cancer cell lines. For the A549 (lung) and MDA-MB-231 (breast) cancer cell lines, the IC50 values of the complexes were 288- to 14-fold lower when compared to cisplatin. Furthermore, the complexes were selective for the A549 and MDA-MB-231 cancer cell lines compared to the MRC-5 nontumor cell line. The multitarget character of the complexes was investigated by using calf thymus DNA (CT DNA), human serum albumin, and human topoisomerase IB (hTopIB). The complexes potently inhibited hTopIB. In particular, complex [Ru(dmp)(dppe)2]PF6 (Ru3), bearing the 4,6-diamino-2-mercaptopyrimidine (dmp) ligand, effectively inhibited hTopIB by acting on both the cleavage and religation steps of the catalytic cycle of this enzyme. Molecular docking showed that the Ru1-Ru5 complexes have binding affinity by active sites on the hTopI and hTopI-DNA, mainly via π-alkyl and alkyl hydrophobic interactions, as well as through hydrogen bonds. Complex Ru3 displayed significant antitumor activity against murine melanoma in mouse xenograph models, but this complex did not damage DNA, as revealed by Ames and micronucleus tests.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , DNA Topoisomerases Tipo I/metabolismo , Fosfinas/farmacologia , Rutênio/farmacologia , Inibidores da Topoisomerase I/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligantes , Fosfinas/química , Rutênio/química , Inibidores da Topoisomerase I/síntese química , Inibidores da Topoisomerase I/química , Células Tumorais Cultivadas
4.
Angew Chem Int Ed Engl ; 60(29): 15891-15898, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-33961724

RESUMO

Although swarming motility and biofilms are opposed collective behaviors, both contribute to bacterial survival and host colonization. Pseudovibrio bacteria have attracted attention because they are part of the microbiome of healthy marine sponges. Two-thirds of Pseudovibrio genomes contain a member of a nonribosomal peptide synthetase-polyketide synthase gene cluster family, which is also found sporadically in Pseudomonas pathogens of insects and plants. After developing reverse genetics for Pseudovibrio, we isolated heptapeptides with an ureido linkage and related nonadepsipeptides we termed pseudovibriamides A and B, respectively. A combination of genetics and imaging mass spectrometry experiments showed heptapetides were excreted, promoting motility and reducing biofilm formation. In contrast to lipopeptides widely known to affect motility/biofilms, pseudovibriamides are not surfactants. Our results expand current knowledge on metabolites mediating bacterial collective behavior.


Assuntos
Peptídeos/metabolismo , Poríferos/genética , Poríferos/metabolismo , Animais , Família Multigênica/genética , Peptídeo Sintases/genética , Peptídeo Sintases/metabolismo , Policetídeo Sintases/genética , Policetídeo Sintases/metabolismo , Simbiose
5.
Environ Sci Pollut Res Int ; 28(31): 42670-42682, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33818727

RESUMO

The International Agency for Research on Cancer (IARC) classifies benzene in group 1 (carcinogenic to humans). Particulate matter (PM) has recently also been classified in this category. This was an advance toward prioritizing the monitoring of particles in urban areas. The aim of the present study was to assess levels of PM2.5 and BTEX (benzene, toluene, ethylbenzene, and xylene), the influence of meteorological variables, the planetary boundary layer (PBL), and urban variables as well as risks to human health in the city of Fortaleza, Brazil, in the wet and dry periods. BTEX compounds were sampled using the 1501 method of NIOSH and determined by GC-HS-PID/FID. PM2.5 was monitored using an air sampling pump with a filter holder and determined by the gravimetric method. Average concentrations of BTEX ranged from 1.6 to 45.5 µg m-3, with higher values in the wet period, which may be explained by the fact that annual distribution is influenced by meteorological variables and the PBL. PM2.5 levels ranged from 4.12 to 33.0 µg m-3 and 4.18 to 86.58 µg m-3 in the dry and wet periods, respectively. No seasonal pattern was found for PM2.5, probably due to the influence of meteorological variables, the PBL, and urban variables. Cancer risk ranged from 2.46E-04 to 4.71E-03 and 1.72E-04 to 2.01E-03 for benzene and from 3.07E-06 to 7.04E-05 and 3.08E-06 to 2.85E-05 for PM2.5 in the wet and dry periods, respectively. Cancer risk values for benzene were above the acceptable limit established by the international regulatory agency in both the dry and wet periods. The results obtained of the noncarcinogenic risks for the compounds toluene, ethylbenzene, and xylene were within the limits of acceptability. The findings also showed that the risk related to PM is always greater among smokers than nonsmokers.


Assuntos
Poluentes Atmosféricos , Material Particulado , Poluentes Atmosféricos/análise , Benzeno/análise , Derivados de Benzeno/análise , Brasil , Monitoramento Ambiental , Humanos , Material Particulado/análise , Tolueno/análise , Xilenos/análise
6.
Braz J Infect Dis ; 25(2): 101542, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33587923

RESUMO

In response to the Zika epidemics in Brazil, the ZDC molecular assay (Bio-Manguinhos) was developed and registered at the Brazilian Regulatory Agency of Health Surveillance - ANVISA. The circulation of Zika (ZIKV) Dengue (DENV) and Chikungunya (CHIKV) viruses and their clinical similarities are challenges to correctly diagnose these viruses. The simultaneous detection of ZIKV, DENV and CHIKV is an important tool for diagnosis and surveillance. Here, we present the analytical and clinical performance evaluation of ZDC molecular assay (Bio-Manguinhos) at the public health laboratories three years after its registration at ANVISA. The clinical performance demonstrates the ZDC molecular assay (Bio-Manguinhos) has 100% sensitivity and 100% specificity to detect and discriminate ZIKV, CHIKV, and DENV from clinical plasma samples. The ZDC molecular assay (Bio-Manguinhos) results were highly reproducible and no cross-reactivity was seen during testing with a panel of other infectious agents. In conclusion, the ZDC molecular assay (Bio-Manguinhos) is an accurate and reliable tool to monitor Zika, dengue and chikungunya infections in countries like Brazil with simultaneous circulation of the three viruses.


Assuntos
Febre de Chikungunya , Vírus Chikungunya , Vírus da Dengue , Dengue , Infecção por Zika virus , Zika virus , Brasil , Febre de Chikungunya/diagnóstico , Vírus Chikungunya/genética , Dengue/diagnóstico , Vírus da Dengue/genética , Humanos , Laboratórios , Zika virus/genética , Infecção por Zika virus/diagnóstico
7.
Br J Haematol ; 192(5): 922-931, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33476407

RESUMO

Sickle cell anaemia (SCA) is a debilitating genetic haemoglobinopathy predominantly affecting the disenfranchised strata of society in Africa and the Americas. The most common pharmacological treatment for this disease is the administration of hydroxycarbamide (HC) for which questions remain regarding its mechanism of action, efficacy and long-term toxicity specifically in paediatric individuals. A multiplatform metabolomics approach was used to assess the metabolome of plasma samples from a population of children and adolescents with SCA with and without HC treatment along with non-SCA individuals. Fifty-three metabolites were identified by ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) and 1 H nuclear magnetic resonance (NMR) with a predominance of membrane lipids, amino acids and organic acids. The partial least-squares discriminant analysis (PLS-DA) analysis allowed a clear discrimination between the different studied groups, revealing clear effects of the HC treatment in the patients' metabolome including rescue of specific metabolites to control levels. Increased creatine/creatinine levels under HC treatment suggests a possible increase in the arginine pool and increased NO synthesis, supporting existing models for HC action in SCA. The metabolomics results extend the current knowledge on the models for SCA pathophysiology including impairment of Lands' cycle and increased synthesis of sphingosine 1-phosphate. Putative novel biomarkers are suggested.


Assuntos
Anemia Falciforme/sangue , Antidrepanocíticos/uso terapêutico , Hidroxiureia/uso terapêutico , Metabolômica , Ácidos/sangue , Síndrome Torácica Aguda/etiologia , Adolescente , Aminoácidos/sangue , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/farmacologia , Arteriopatias Oclusivas/etiologia , Biomarcadores , Butiratos/sangue , Criança , Cromatografia Líquida de Alta Pressão , Creatina/sangue , Creatinina/sangue , Feminino , Humanos , Hidroxiureia/farmacologia , Lisofosfolipídeos/sangue , Masculino , Espectrometria de Massas , Lipídeos de Membrana/sangue , Modelos Biológicos , Ressonância Magnética Nuclear Biomolecular , Esfingosina/análogos & derivados , Esfingosina/sangue
8.
J Nat Prod ; 84(3): 790-796, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33371682

RESUMO

Metabolomics analysis detected tambjamine alkaloids in aqueous and EtOAc extracts of the marine invertebrates Virididentula dentata, Tambja stegosauriformis, Tambja brasiliensis, and Roboastra ernsti. Among several tambjamines, the new amino acid derivatives tambjamines M-O (17-19) were identified by Marfey's advanced analysis, UPLC-MS/MS analyses, and total synthesis. The tambjamine diversity increased from the bryozoan V. dentata to its nudibranch predators T. stegosauriformis and T. brasiliensis and attained a higher diversity in R. ernsti, the nudibranch that preys upon T. stegosauriformis and T. brasiliensis. The total tambjamine content also increases among the trophic levels, probably due to biomagnification. Tambjamines A (1), C (3), and D (4) are the major metabolites in the tissues of V. dentata, T. stegosauriformis, T. brasiliensis, and R. ernsti and are likely the main chemical defenses of these marine invertebrates.

9.
Braz. j. infect. dis ; 25(2): 101542, 2021. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1278571

RESUMO

ABSTRACT In response to the Zika epidemics in Brazil, the ZDC molecular assay (Bio-Manguinhos) was developed and registered at the Brazilian Regulatory Agency of Health Surveillance - ANVISA. The circulation of Zika (ZIKV) Dengue (DENV) and Chikungunya (CHIKV) viruses and their clinical similarities are challenges to correctly diagnose these viruses. The simultaneous detection of ZIKV, DENV and CHIKV is an important tool for diagnosis and surveillance. Here, we present the analytical and clinical performance evaluation of ZDC molecular assay (Bio-Manguinhos) at the public health laboratories three years after its registration at ANVISA. The clinical performance demonstrates the ZDC molecular assay (Bio-Manguinhos) has 100% sensitivity and 100% specificity to detect and discriminate ZIKV, CHIKV, and DENV from clinical plasma samples. The ZDC molecular assay (Bio-Manguinhos) results were highly reproducible and no cross-reactivity was seen during testing with a panel of other infectious agents. In conclusion, the ZDC molecular assay (Bio-Manguinhos) is an accurate and reliable tool to monitor Zika, dengue and chikungunya infections in countries like Brazil with simultaneous circulation of the three viruses.

10.
Inorg Chem ; 59(20): 15004-15018, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-32997499

RESUMO

In this paper, a series of new ruthenium complexes of the general formula [Ru(NS)(dpphpy)(dppb)]PF6 (Ru1-Ru3), where dpphpy = diphenyl-2-pyridylphosphine, NS ligands = 2-thiazoline-2-thiol (tzdt, Ru1), 2-mercaptopyrimidine (pySm, Ru2), and 4,6-diamino-2-mercaptopyrimidine (damp, Ru3), and dppb = 1,4-bis(diphenylphosphino)butane, were synthesized and characterized by elemental analysis, spectroscopic techniques (IR, UV/visible, and 1D and 2D NMR), and X-ray diffraction. In the characterization, the correlation between the phosphorus atoms and their respective aromatic hydrogen atoms of the compounds in the assignment stands outs, by 1H-31P HMBC experiments. The compounds show anticancer activities against A549 (lung) and MDA-MB-231 (breast) cancer cell lines, higher than the clinical drug cisplatin. All of the complexes are more cytotoxic against the cancer cell lines than against the MRC-5 (lung) and MCF-10A (breast) nontumorigenic human cell lines. For A549 tumor cells, cell cycle analysis upon treatment with Ru2 showed that it inhibits the mitotic phase because arrest was observed in the Sub-G1 phase. Additionally, the compound induces cell death by an apoptotic pathway in a dose-dependent manner, according to annexin V-PE assay. The multitargeted character of the compounds was investigated, and the biomolecules were DNA, topoisomerase IB, and proteasome, as well as the fundamental biomolecule in the pharmacokinetics of drugs, human serum albumin. The experimental results indicate that the complexes do not target DNA in the cells. At low concentrations, the compounds showed the ability to partially inhibit the catalytic activity of topoisomerase IB in the process of relaxation of the DNA plasmid. Among the complexes assayed in cultured cells, complex Ru3 was able to diminish the proteasomal chymotrypsin-like activity to a greater extent.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , DNA Topoisomerases Tipo I/metabolismo , Inibidores de Proteassoma/farmacologia , Inibidores da Topoisomerase I/farmacologia , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Fosfinas/síntese química , Fosfinas/farmacologia , Inibidores de Proteassoma/síntese química , Rutênio/química , Compostos de Sulfidrila/síntese química , Compostos de Sulfidrila/farmacologia , Inibidores da Topoisomerase I/síntese química
11.
Biomed Res Int ; 2020: 1803515, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908871

RESUMO

Despite several available methodologies for Chagas disease (CD) serological screening, the main limitation of chronic CD diagnosis is the lack of effective tools for large-scale screening and point-of-care diagnosis to be used in different CD epidemiological scenarios. Taking into account that developing such a diagnostic tool will significantly improve the ability to identify CD carriers, we aimed at performing a proof-of-concept study (phase I study) to assess the use of these proteins in a point-of-care platform using serum samples from different geographical settings of Brazil and distinct clinical presentations. The diagnostic accuracy study was conducted on a panel of two WHO International Standards (IS) and 14 sera from T. cruzi-positive and 16 from T. cruzi-negative individuals. The results obtained with the test strips were converted to digital images, allowing quantitative comparison expressed as a relative band intensity ratio (RBI). The diagnostic potential and performance were also determined. Regardless of the geographical origin or clinical presentation, all sera with T. cruzi antibodies returned positive both for IBMP-8.1 and IBMP-8.4 chimeric antigens. The area under the ROC curve (AUC) values was 100% for both antigens, demonstrating an outstanding overall diagnostic accuracy (100%). Based on the data, we believe that the lateral flow assays based on these antigens are promising methodologies for screening CD.


Assuntos
Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/imunologia , Doença de Chagas/diagnóstico , Imunoensaio/métodos , Trypanosoma cruzi/imunologia , Antígenos de Protozoários/genética , Brasil , Doença de Chagas/imunologia , Doença de Chagas/parasitologia , Cromatografia de Afinidade/instrumentação , Cromatografia de Afinidade/métodos , Ensaio de Imunoadsorção Enzimática/instrumentação , Ensaio de Imunoadsorção Enzimática/métodos , Desenho de Equipamento , Humanos , Imunoensaio/instrumentação , Testes Imediatos , Estudo de Prova de Conceito , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Trypanosoma cruzi/genética
12.
J Nat Prod ; 83(6): 1784-1793, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32525315

RESUMO

Herein reported are results of the chemical and biological investigation of red propolis collected at the Brazilian Northeast coastline. New propolones A-D (1-4), with a 3-{3-[(2-phenylbenzofuran-3-yl)methyl]phenyl}chromane skeleton; propolonones A-C (5-7), with a 3-[3-(3-benzylbenzofuran-2-yl)phenyl]chromane skeleton; and propolol A (8), with a 6-(3-benzylbenzofuran-2-yl)-3-phenylchromane skeleton, were isolated as constituents of Brazilian red propolis by cytotoxicity-guided assays and structurally identified by analysis of their spectroscopic data. Propolone B (2) and propolonone A (5) display significant cytotoxic activities against an ovarian cancer cell line expressing a multiple drug resistance phenotype when compared with doxorubicin.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Própole/química , Antibióticos Antineoplásicos/farmacologia , Brasil , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Neoplasias Ovarianas/tratamento farmacológico
13.
Bioorg Chem ; 100: 103921, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32464403

RESUMO

Enterococci are gram-positive, widespread nosocomial pathogens that in recent years have developed resistance to various commonly employed antibiotics. Since finding new infection-control agents based on secondary metabolites from organisms has proved successful for decades, natural products are potentially useful sources of compounds with activity against enterococci. Herein are reported the results of a natural product library screening based on a whole-cell assay against a gram-positive model organism, which led to the isolation of a series of anacardic acids identified by analysis of their spectroscopic data and by chemical derivatizations. Merulinic acid C was identified as the most active anacardic acid derivative obtained against antibiotic-resistant enterococci. Fluorescence microscopy analyses showed that merulinic acid C targets the bacterial membrane without affecting the peptidoglycan and causes rapid cellular ATP leakage from cells. Merulinic acid C was shown to be synergistic with gentamicin against Enterococcus faecium, indicating that this compound could inspire the development of new antibiotic combinations effective against drug-resistant pathogens.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Enterococcus faecium/efeitos dos fármacos , Gentamicinas/farmacologia , Sinergismo Farmacológico , Enterococcus faecium/crescimento & desenvolvimento , Enterococcus faecium/metabolismo , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Hidroxibenzoatos/farmacologia
14.
Metabolites ; 10(2)2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32098128

RESUMO

This study investigated the chronic effect of inspiratory muscle training (IMT) on the human serum metabolome in healthy male recreational cyclists. Using a randomized, parallel group design, twenty-eight participants were randomized to three IMT groups: low intensity (LI, n = 7); moderate intensity (MI, n = 10); and high intensity (HI, n = 11). The IMT was performed for 11 weeks. Another group of participants under the same conditions, who did not perform the IMT but participated in all procedures, was included as controls (CG, n = 6). Blood samples were collected one week before and after 11 weeks of IMT and analyzed for metabolite shifts using 1H NMR. Statistical analysis included a 4 (group) × 2 (time) repeated measures ANOVA using the general linear model (GLM), and multivariate principal component analysis (PCA). Untargeted metabolomics analysis of serum samples identified 22 metabolites, including amino acids, lipids, and tricarboxylic acid cycle intermediates. Metabolites shifts did not differ between groups, indicating that IMT at three intensity levels did not alter the serum metabolome relative to the control group. These results reveal novel insights into the metabolic effects of the IMT and are consistent with the results from other studies showing negligible chronic alterations in the serum metabolome in response to physical training.

15.
J Nat Prod ; 83(1): 55-65, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31895573

RESUMO

A new method of screening was developed to generate 770 organic and water-soluble fractions from extracts of nine species of marine sponges, from the growth media of 18 species of marine-derived fungi, and from the growth media of 13 species of endophytic fungi. The screening results indicated that water-soluble fractions displayed significant bioactivity in cytotoxic, antibiotic, anti-Leishmania, anti-Trypanosoma cruzi, and inhibition of proteasome assays. Purification of water-soluble fractions from the growth medium of Penicillium solitum IS1-A provided the new glutamic acid derivatives solitumine A (1), solitumine B (2), and solitumidines A-D (3-6). The structures of compounds 1-6 have been established by analysis of spectroscopic data, chemical derivatizations, and vibrational circular dichroism calculations. Although no biological activity could be observed for compounds 1-6, the new structures reported for 1-6 indicate that the investigation of water-soluble natural products represents a relevant strategy in finding new secondary metabolites.


Assuntos
Glutamatos/química , Regiões Antárticas , Fungos/química , Estrutura Molecular , Penicillium/química , Água
16.
Genet Mol Biol ; 43(1): e20180237, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31644681

RESUMO

Hepatitis C virus (HCV) infection is a worldwide health problem. Nowadays, direct-acting antiviral agents (DAAs) are the main treatment for HCV; however, the high level of virus variability leads to the development of resistance-associated variants (RAVs). Thus, assessing RAVs in infected patients is important for monitoring treatment efficacy. The aim of our study was to investigate the presence of naturally occurring resistance mutations in HCV NS3 and NS5 regions in treatment-naïve patients. Ninety-six anti-HCV positive serum samples from blood donors at the Center of Hematology and Hemotherapy of Santa Catarina State (HEMOSC) were collected retrospectively in 2013 and evaluated in this study. HCV 1a (37.9%), 1b (25.3%), and 3a (36.8%) subtypes were found. The frequency of patients with RAVs in our study was 6.9%. The HCV NS5b sequencing reveled 1 sample with L320F mutation and 4 samples with the C316N/R polymorphism. The analysis of the NS3 region revealed the D168A/G/T (3.45%), S122G (1.15%), and V55A (2.3%) mutations. All samples from genotype 3a (36.8%) presented the V170 I/V non-synonymous mutation. In conclusion, we have shown that mutations in NS3 and NS5b genes are present in Brazilian isolates from therapy-naïve HCV patients.

17.
Antioxidants (Basel) ; 8(12)2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31816926

RESUMO

Orange peel is a by-product produced in large amounts that acts as a source of natural pigments such as carotenoids. Xanthophylls, the main carotenoid class found in citrus fruit, can be present in its free form or esterified with fatty acids, forming esters. This esterification modifies the compound's chemical properties, affecting their bioavailability in the human body, and making it important to characterize the native carotenoid composition of food matrices. We aimed to evaluate the non-saponified carotenoid extracts of orange peel (cv. Pera) obtained using alternative green approaches: extraction with ionic liquid (IL), analyzed by high performance liquid chromatography coupled to a diode array detector with atmospheric pressure chemical ionization and mass spectrometry HPLC-DAD-APCI-MS, and supercritical fluid extraction (SFE), followed by supercritical fluid chromatography with atmospheric pressure chemical ionization and triple quadrupole mass spectrometry detection (SFC-APCI/QqQ/MS) in an online system. Both alternative green methods were successfully applied, allowing the total identification of five free carotenoids, one apocarotenoid, seven monoesters, and 11 diesters in the extract obtained with IL and analyzed by HPLC-DAD-APCI-MS, and nine free carotenoids, six carotenoids esters, 19 apocarotenoids, and eight apo-esters with the SFE-SFC-APCI/QqQ/MS approach, including several free apocarotenoids and apocarotenoid esters identified for the first time in oranges, and particularly in the Pera variety, which could be used as a fruit authenticity parameter.

18.
Rev. bras. farmacogn ; 29(6): 715-719, Nov.-Dec. 2019. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1057861

RESUMO

ABSTRACT Chemical investigation of the aqueous fraction of the ethanol extract from the Brazilian endemic marine sponge Clathria (Clathria) nicoleae Vieira de Barros, Santos & Pinheiro, 2013, Microcionidae, sampled from a 55 m deep rhodolith bed at the Amazon River mouth, led to the isolation of a new hexapeptide, clathriamide (1). HP-20 resin was used to capture compound 1 from the aqueous fraction, which was purified by additional chromatographic steps. The absolute configuration of the amino acids of 1 was determined by advanced Marfey's analysis using 5-fluoro-2,4-dinitrophenyl-Nα-L-tryptophanamide. The amino acid derivatives analyzed by ultra-performance liquid chromatography coupled to a mass spectrometry using a C8 column enabled a good chromatographic resolution of L-Ile and L-allo-Ile, previously unfeasible using C18 column.

19.
Dalton Trans ; 48(18): 6026-6039, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-30724926

RESUMO

In this paper, four new ruthenium complexes, [Ru(N-S)(dppm)2]PF6 (1), [Ru(N-S)(dppe)2]PF6 (2), [Ru(N-S)2(dppp)] (3) and [Ru(N-S)2(PPh3)2] (4) [dppm = 1,1-bis(diphenylphosphino)methane, dppe = 1,2-bis(diphenylphosphino)ethane, dppp = 1,3-bis(diphenylphosphino)propane, PPh3 = triphenylphosphine and N-S = 2-mercaptopyrimidine anion] were synthesized and characterized using spectroscopy techniques, molar conductance, elemental analysis, electrochemical techniques and X-ray diffraction. The DNA binding studies were investigated using voltammetry and spectroscopy techniques. The results show that all complexes exhibit a weak interaction with DNA. HSA interaction with the complexes was studied using fluorescence emission spectroscopy, where the results indicate a spontaneous interaction between the species by a static quenching mechanism. The cytotoxicity of the complexes was evaluated against A549, MDA-MB-231 and HaCat cells by MTT assay. Complexes (1) and (2), which are very active against triple negative MDA-MB-231, were subjected to further biological tests with this cell line. The cytotoxic activity triggered by the complexes was confirmed by clonogenic assay. Cell cycle analyses demonstrated marked anti-proliferative effects, especially at the G0/G1 and S phases. The morphological detection of apoptosis and necrosis - HO/PI and Annexin V-FITC/PI assay, elucidated that the type of cell death triggered by these complexes was probably by apoptosis. The in vivo toxicological assessment performed on zebrafish embryos revealed that complexes (1) and (2) did not present embryotoxic or toxic effects during embryonic and larval development showing that they are promising new prototypes of safer and more effective drugs for triple negative breast cancer treatment.


Assuntos
Antineoplásicos/síntese química , Complexos de Coordenação/síntese química , Substâncias Intercalantes/síntese química , Pirimidinas/química , Rutênio/química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/toxicidade , DNA/metabolismo , Desenho de Fármacos , Técnicas Eletroquímicas/métodos , Humanos , Substâncias Intercalantes/farmacologia , Substâncias Intercalantes/toxicidade , Estrutura Molecular , Relação Estrutura-Atividade , Termodinâmica , Peixe-Zebra/embriologia
20.
Adv synth catal, v. 361, n. 13, p. 3163-3172, apr. 2019
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-2838

RESUMO

The iron(III)-promoted synthesis of densely-substituted 4H-chalcogenchromene from organochalcogen propargylamines in the presence of diaryl dichalcogenides is reported. Subsequent C2-functionalization with electrophiles and potassium trifluoroborate salts via Suzuki-Miyaura coupling reaction are also presented. A plausible mechanism based on HRMS experiments is proposed and discussed.

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