Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 62
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Oncol ; 2023: 7797710, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36814559

RESUMO

N6-methyladenosine (m6A) modification is a common epigenetic modification. It is reported that lncRNA can be regulated by m6A modification. Previous studies have shown that lncRNAs associated with m6A regulation (m6A-lncRNAs) serve as ideal prognostic biomarkers. However, whether lncRNAs are involved in m6A modification in colon adenocarcinoma (COAD) needs further exploration. The objective of this study was to construct an m6A-lncRNAs-based signature for patients with COAD. We obtained the RNA sequencing data and clinical information from The Cancer Genome Atlas (TCGA). Pearson correlation analysis was employed to recognize lncRNAs associated with m6A regulation (m6A-lncRNAs). 24 prognostic m6A-lncRNAs was identified by univariate Cox regression analysis. Gene set enrichment analysis (GSAE) was used to investigate the potential cellular pathways and biological processes. We have also explored the relationship between immune infiltrate levels and m6A-lncRNAs. Then, a predictive signature based on the expression of 13 m6A-lncRNAs was constructed by the Lasso regression algorithm, including UBA6-AS1, AC139149.1, U91328.1, AC138207.5, AC025171.4, AC008760.1, ITGB1-DT, AP001619.1, AL391422.4, AC104532.2, ZEB1-AS1, AC156455.1, and AC104819.3. ROC curves and K M survival curves have shown that the risk score has a well-predictive ability. We also set up a quantitative nomogram on the basis of risk score and prognosis-related clinical characteristics. In summary, we have identified some m6A-lncRNAs that correlated with prognosis and tumor immune microenvironment in COAD. In addition, a potential alternative signature based on the expression of m6A-lncRNAs was provided for the management of COAD patients.

2.
Huan Jing Ke Xue ; 41(5): 2137-2148, 2020 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608831

RESUMO

To analyze the spatial-temporal distribution and sedimentation characteristics of suspended solids in reservoirs, high-frequency monitoring of a sediment trap and buoy, combined with three-dimensional water sampling, was conducted and analyzed in Xin'anjiang Reservoir for a year. The results showed that the turbidity data of the buoy has significant correlation with rainfall, inflow, and suspended solids (SS), particularly for SS (P<0.01, R2=0.86). There is an obvious spatial difference in SS between spring and summer, when the rainfall season occurs (river area > transition area > lake area). However, there is little difference in SS concentration between autumn and winter. There is a spatial trend of river area > transition area > lake area (with rates of 27.82, 4.34, and 0.26 g·(m2·d)-1, respectively), and a temporal trend of spring and summer > autumn and winter. The sedimentation flux of the whole lake is 2.57×106 t·a-1 combined with the investigation of the four-season SS at 60 points across the whole lake, and the settlement flux in spring and summer is higher than that in autumn and winter. The contents of particulate nitrogen (PN) in JK, XJS, and DB were 6812, 15886, and 21986 mg·kg-1, and the particulate phosphorus (PP) contents were 2545, 3269, and 3077 mg·kg-1, respectively. Statistical analysis shows that there is a good exponential relationship between moderate rainfall and turbidity growth rate in the river area of the reservoir (R2=0.81). Moreover, the continuous heavy rainfall affects turbidity in river area, but has little effect on the transition area. The concentration of SS has a good exponential decay with distance from the river to the dam (R2=0.84), especially in spring and summer. Research shows that the average annual deposition rate in Xin'anjiang Reservoir is 0.07%, lower than other large reservoirs in the country; however, there are certain risks in front of the dam because the nutrient sediments are high. The results suggest that reservoir managers should pay attention to water and soil conservation in the watershed to reduce the impact of rainfall on reservoir water quality. Meanwhile, the potential nutrient internal release risk in the downstream area before the dam should be considered.

3.
Molecules ; 25(2)2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31936367

RESUMO

Schisantherin A is an active ingredient originating from Schisandra chinensis (Turcz.) which has hepatoprotective and anti-oxidation activities. In this study, in vitro metabolisms investigated on rat liver microsomes (RLMs) and in vivo metabolisms explored on male Sprague Dawley rats of Schisantherin A were tested, respectively. The metabolites of Schisantherin A were identified using ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). Based on the method, 60 metabolites were successfully identified and structurally characterized including 48 phase-I and 12 phase-II metabolites. Among the metabolites, 45 metabolites were reported for the first time. Moreover, 56 and eight metabolites were detected in urine and bile and 19 metabolites were identified in rats' plasma. It demonstrated that hepatic and extra-hepatic metabolic pathways were both involved in Schisantherin A biotransformation in rats. Five in vitro metabolites were structurally characterized for the first time. The results indicated that the metabolic pathways mainly include oxidation, reduction, methylation, and conjugation with glucuronide, taurine, glucose, and glutathione groups. This study provides a practical strategy for rapidly screening and identifying metabolites, and the results provide basic data for future pharmacological and toxicology studies of Schisantherin A and other lignin ingredients.


Assuntos
Ciclo-Octanos/análise , Ciclo-Octanos/metabolismo , Dioxóis/análise , Dioxóis/metabolismo , Avaliação Pré-Clínica de Medicamentos , Lignanas/análise , Lignanas/metabolismo , Metaboloma , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão , Ciclo-Octanos/química , Dioxóis/química , Íons , Lignanas/química , Masculino , Redes e Vias Metabólicas , Metabolômica , Oxirredução , Ratos Sprague-Dawley
4.
Theranostics ; 9(18): 5298-5314, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410216

RESUMO

Rationale: Hypoxia has been proved to contribute to aggressive phenotype of cancers, while functional and regulatory mechanism of long noncoding RNA (lncRNA) in the contribution of hypoxia on pancreatic cancer (PC) tumorigenesis is incompletely understood. The aim of this study was to uncover the regulatory and functional roles for hypoxia-induced lncRNA-MTA2TR (MTA2 transcriptional regulator RNA, AF083120.1) in the regulation of PC tumorigenesis. Methods: A lncRNA microarray confirmed MTA2TR expression in tissues of PC patients. The effects of MTA2TR on proliferation and metastasis of PC cells and xenograft models were determined, and the key mechanisms by which MTA2TR promotes PC were further dissected. Furthermore, the expression and regulation of MTA2TR under hypoxic conditions in PC cells were assessed. We also assessed the correlation between MTA2TR expression and PC patient clinical outcomes. Results: We found that metastasis associated protein 2 (MTA2) transcriptional regulator lncRNA (MTA2TR) was overexpressed in PC patient tissues relative to paired noncancerous tissues. Furthermore, we found that depletion of MTA2TR significantly inhibited PC cell proliferation and invasion both in vitro and in vivo. We further demonstrated that MTA2TR transcriptionally upregulates MTA2 expression by recruiting activating transcription factor 3 (ATF3) to the promoter area of MTA2. Consequentially, MTA2 can stabilize the HIF-1α protein via deacetylation, which further activates HIF-1α transcriptional activity. Interestingly, our results revealed that MTA2TR is transcriptionally regulated by HIF-1α under hypoxic conditions. Our clinical samples further indicated that the overexpression of MTA2TR was correlated with MTA2 upregulation, as well as with reduced overall survival (OS) in PC patients. Conclusions: These results suggest that feedback between MTA2TR and HIF-1α may play a key role in regulating PC tumorigenesis, thus potentially highlighting novel avenues PC treatment.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Pancreáticas/genética , RNA Longo não Codificante/metabolismo , Acetilação , Fator 3 Ativador da Transcrição/metabolismo , Animais , Hipóxia Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Neoplasias Pancreáticas/patologia , Prognóstico , Regiões Promotoras Genéticas , Estabilidade Proteica , RNA Longo não Codificante/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transcrição Gênica
5.
Proc Natl Acad Sci U S A ; 116(10): 4200-4205, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30782805

RESUMO

Each year influenza virus infections cause hundreds of thousands of deaths worldwide and a significant level of morbidity with major economic burden. At the present time, vaccination with inactivated virus vaccine produced from embryonated chicken eggs is the most prevalent method to prevent the infections. However, current influenza vaccines are only effective against closely matched circulating strains and must be updated and administered yearly. Therefore, generating a vaccine that can provide broad protection is greatly needed for influenza vaccine development. We have previously shown that vaccination of the major surface glycoprotein hemagglutinin (HA) of influenza virus with a single N-acetylglucosamine at each of the N-glycosylation sites [monoglycosylated HA (HAmg)] can elicit better cross-protection compared with the fully glycosylated HA (HAfg). In the current study, we produced monoglycosylated inactivated split H1N1 virus vaccine from chicken eggs by the N-glycosylation process inhibitor kifunensine and the endoglycosidase Endo H, and intramuscularly immunized mice to examine its efficacy. Compared with vaccination of the traditional influenza vaccine with complex glycosylations from eggs, the monoglycosylated split virus vaccine provided better cross-strain protection against a lethal dose of virus challenge in mice. The enhanced antibody responses induced by the monoglycosylated vaccine immunization include higher neutralization activity, higher hemagglutination inhibition, and more HA stem selectivity, as well as, interestingly, higher antibody-dependent cellular cytotoxicity. This study provides a simple and practical procedure to enhance the cross-strain protection of influenza vaccine by removing the outer part of glycans from the virus surface through modifications of the current egg-based process.


Assuntos
Proteção Cruzada/imunologia , Ovos , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Vacinação , Animais , Galinhas/anormalidades , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Hemaglutininas/imunologia , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/prevenção & controle , Injeções Intramusculares , Manosil-Glicoproteína Endo-beta-N-Acetilglucosaminidase/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia
6.
Cancer Res ; 79(7): 1398-1412, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30563888

RESUMO

Cancer cells are known to undergo metabolic reprogramming, such as glycolysis and glutamine addiction, to sustain rapid proliferation and metastasis. It remains undefined whether long noncoding RNAs (lncRNA) coordinate the metabolic switch in pancreatic cancer. Here we identify a nuclear-enriched antisense lncRNA of glutaminase (GLS-AS) as a critical regulator involved in pancreatic cancer metabolism. GLS-AS was downregulated in pancreatic cancer tissues compared with noncancerous peritumor tissues. Depletion of GLS-AS promoted proliferation and invasion of pancreatic cancer cells both in vitro and in xenograft tumors of nude mice. GLS-AS inhibited GLS expression at the posttranscriptional level via formation of double stranded RNA with GLS pre-mRNA through ADAR/Dicer-dependent RNA interference. GLS-AS expression was transcriptionally downregulated by nutrient stress-induced Myc. Conversely, GLS-AS decreased Myc expression by impairing the GLS-mediated stability of Myc protein. These results imply a reciprocal feedback loop wherein Myc and GLS-AS regulate GLS overexpression during nutrient stress. Ectopic overexpression of GLS-AS inhibited proliferation and invasion of pancreatic cancer cells by repressing the Myc/GLS pathway. Moreover, expression of GLS-AS and GLS was inversely correlated in clinical samples of pancreatic cancer, while low expression of GLS-AS was associated with poor clinical outcomes. Collectively, our study implicates a novel lncRNA-mediated Myc/GLS pathway, which may serve as a metabolic target for pancreatic cancer therapy, and advances our understanding of the coupling role of lncRNA in nutrition stress and tumorigenesis.Significance: These findings show that lncRNA GLS-AS mediates a feedback loop of Myc and GLS, providing a potential therapeutic target for metabolic reprogramming in pancreatic cancer.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/7/1398/F1.large.jpg.See related commentary by Mafra and Dias, p. 1302.


Assuntos
Neoplasias Pancreáticas/genética , RNA Longo não Codificante/genética , Animais , Glutaminase , Camundongos , Camundongos Nus , Nutrientes
7.
Oncogene ; 37(44): 5811-5828, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29970904

RESUMO

The contribution of long noncoding RNAs (lncRNAs) to pancreatic cancer progression and the regulatory mechanisms of their expression are attractive areas. In the present study, the overexpression of lncRNA-BX111887 (BX111) in pancreatic cancer tissues was detected by microarray and further validated in a cohort of pancreatic cancer tissues. We further demonstrated that knockdown or overexpression of BX111 dramatically repressed or enhanced proliferation and invasion of pancreatic cancer cells. Mechanically, BX111 activated transcription of ZEB1, a key regulator for epithelia-mesenchymal transition (EMT), via recruiting transcriptional factor Y-box protein (YB1) to its promoter region. Moreover, we revealed that BX111 transcription was induced by hypoxia-inducible factor (HIF-1α) in response to hypoxia. In addition, BX111 contributed to the hypoxia-induced EMT of pancreatic cells by regulating expression of ZEB1 and its downstream proteins E-cadherin and MMP2. Coincidence with in vitro results, BX111 depletion effectively inhibited growth and metastasis of xenograft tumor in vivo. The clinical samples of pancreatic cancer further confirmed a positive association between BX111 and ZEB1. Moreover, high BX111 expression was correlated with late TNM stage, lymphatic invasion and distant metastasis, as well as short overall survival time in patients. Taken together, our findings implicate a hypoxia-induced lncRNA contributes to metastasis and progression of pancreatic cancer, and suggest BX111 might be applied as a potential biomarker and therapeutic target for pancreatic cancer.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas/genética , RNA Longo não Codificante/fisiologia , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Animais , Hipóxia Celular , Linhagem Celular Tumoral , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/fisiologia , Humanos , Fator 1 Induzível por Hipóxia/genética , Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Metástase Linfática , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/fisiopatologia , Neoplasias Pancreáticas/secundário , RNA Longo não Codificante/metabolismo , Transcrição Gênica , Proteína 1 de Ligação a Y-Box/genética , Proteína 1 de Ligação a Y-Box/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo
8.
Chem Biodivers ; 15(10): e1800261, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29987907

RESUMO

A new class of 1-[(1R,2S)-2-fluorocyclopropyl]ciprofloxacin (CPFX)-1,2,4-triazole-5(4H)-thione hybrids 6a - 6o was designed, synthesized and evaluated for their in vitro antibacterial activities against a panel of clinically important drug-sensitive and drug-resistant Gram-positive and Gram-negative pathogens. Our results revealed that all hybrids 6a - 6o had great potency against the tested strains, especially Gram-negative pathogens. The synthesized hybrids were more potent than the parent 1-[(1R,2S)-2-fluorocyclopropyl]CPFX (1) and comparable to CPFX and levofloxacin against the majority of the tested pathogens, worth to be further investigated.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Ciprofloxacina/análogos & derivados , Ciprofloxacina/farmacologia , Desenho de Fármacos , Triazóis/química , Triazóis/farmacologia , Antibacterianos/síntese química , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Ciprofloxacina/síntese química , Halogenação , Humanos , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , Tionas/síntese química , Tionas/química , Tionas/farmacologia , Triazóis/síntese química
9.
Curr Top Med Chem ; 18(2): 101-113, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29473509

RESUMO

Bis-coumarins have caused great interests in the recent years. These compounds exhibit diverse biological activities which are ascribed to their ability to exert noncovalent interactions with the various active sites in organisms. Some of them such as dicoumarolum and dicoumarol were approved for therapeutic purposes in clinical practice. Encouraged by the above facts, numerous biscoumarin derivatives have been synthesized and screened for their biological activities, and many of them showed promising potency. This review is focused on the biological potential of bis-coumarin derivatives with particular mention of those exhibiting antibacterial, anticoagulant, antiinflammatory, antiviral, anti-parasite and antitumor activities, and their structure-activity relationships are also discussed.


Assuntos
Anti-Infecciosos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Anticoagulantes/farmacologia , Antineoplásicos/farmacologia , Antiparasitários/farmacologia , Cumarínicos/farmacologia , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Anticoagulantes/síntese química , Anticoagulantes/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antiparasitários/síntese química , Antiparasitários/química , Cumarínicos/síntese química , Cumarínicos/química , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
10.
Eur J Med Chem ; 146: 599-612, 2018 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-29407984

RESUMO

Bacterial infections represent a significant health threat globally, and are responsible for the majority of hospital-acquired infections, leading to extensive mortality and burden on global healthcare systems. The second generation fluoroquinolone ciprofloxacin which exhibits excellent antimicrobial activity and pharmacokinetic properties as well as few side effects is introduced into clinical practice for the treatment of various bacterial infections for around 3 decades. The emergency and widely spread of drug-resistant pathogens making ciprofloxacin more and more ineffective, so it's imperative to develop novel antibacterials. Numerous of ciprofloxacin derivatives have been synthesized for seeking for new antibacterials, and some of them exhibited promising potency. This review aims to summarize the recent advances made towards the discovery of ciprofloxacin derivatives as antibacterial agents and the structure-activity relationship of these derivatives was also discussed.


Assuntos
Antibacterianos/farmacologia , Ciprofloxacina/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Ciprofloxacina/síntese química , Ciprofloxacina/química , Relação Dose-Resposta a Droga , Estrutura Molecular , Relação Estrutura-Atividade
11.
Oncogene ; 37(13): 1743-1758, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29343850

RESUMO

Migration and invasion inhibitory protein (MIIP) is recently identified as an inhibitor in tumor development. However, the regulatory mechanism and biological contributions of MIIP in pancreatic cancer (PC) have been not elucidated. In this study, we demonstrated a negative feedback of MIIP and hypoxia-induced factor-1α (HIF-1α), which was mediated by a hypoxia-induced microRNA. Compared with paracarcinoma tissues, MIIP was downregulated in PC tissues. Overexpression of MIIP significantly impeded the proliferation and invasion of PC cells both in vitro and in mouse xenograft models. We further verified MIIP was downregulated under hypoxia in a HIF-1α-mediated manner. Interestingly, although MIIP promoter containing two putative hypoxia response elements (HREs), the chromatin immunoprecipitation (ChIP) and luciferase reporter assays did not support an active interaction between HIF-1α and MIIP promoter. Meanwhile, microRNA array revealed a hypoxia-induced microRNA, miR-646, impaired stability of MIIP mRNA and consequently inhibited its expression by targeting the coding sequence (CDS). Coincidently, knockdown of miR-646 significantly repressed proliferation and invasion ability of PC cells both in vitro and in vivo by upregulating MIIP expression. Besides, ChIP and luciferase reporter assays further validated that HIF-1α activated transcription of miR-646 in hypoxia condition. Therefore, these results suggested HIF-1α indirectly regulated MIIP expression in post-transcriptional level through upregulating miR-646 transcription. Conversely, our results further revealed that MIIP suppressed deacetylase ability of histone deacetylase 6 (HDAC6) to promote the acetylation and degradation of HIF-1α, by which impairing HIF-1α accumulation. What is more, a specific relationship between downregulated MIIP and upregulated miR-646 expression was validated in PC samples. Moreover, the dysregulated miR-646 and MIIP expression was correlated with advanced tumor stage, lymphatic invasion, metastasis and shorter overall survival in PC patients. Together, our results highlight that the reciprocal loop of HIF-1α/miR-646/MIIP might be implemented as an applicable target for pancreatic cancer therapy.


Assuntos
Carcinogênese/genética , Proteínas de Transporte/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , MicroRNAs/fisiologia , Neoplasias Pancreáticas/genética , Adulto , Idoso , Animais , Proliferação de Células/genética , Células Cultivadas , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Hipóxia Tumoral/genética
12.
Curr Top Med Chem ; 18(2): 114-123, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29243579

RESUMO

Malaria still remains one of the leading deadliest diseases throughout the world, leading to around 1 million deaths annually. The emergence and spread of growing resistance to the firstline antimalarials are an alarming the serious problem in malaria control, demanding the need for new drugs more potent than earlier with improved Absorption, Distribution, Metabolism, and Excretion (ADME) profiles. Coumarins, which exhibited various biological properties, also displayed potential in vitro antiplasmodial and in vivo antimalarial activities. Moreover, many of coumarin derivatives have already been used in clinical practice for the treatment of several diseases. Therefore, coumarin derivatives play a pivotal role in medicinal chemistry, also making them promising candidates for the treatment of malaria. This review aims to summarize the recent advances made towards the development of coumarin-containing derivatives as antiplasmodial and antimalarial agents and their structure-activity relationship is also discussed.


Assuntos
Antimaláricos/farmacologia , Antiprotozoários/farmacologia , Cumarínicos/farmacologia , Malária/tratamento farmacológico , Malária/parasitologia , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/síntese química , Antimaláricos/química , Antiprotozoários/síntese química , Antiprotozoários/química , Química Farmacêutica , Cumarínicos/síntese química , Cumarínicos/química , Humanos , Relação Estrutura-Atividade
13.
Curr Top Med Chem ; 17(29): 3219-3231, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29243577

RESUMO

Fungi place a huge burden on global healthcare systems attributed to the fact that fungal infections are responsible for the high morbidity and mortality rates in patients who received stem cell transplantation, antineoplastic chemotherapy, organ transplants or suffered Human Immunodeficiency Virus (HIV) infection. Unfortunately, almost none of the representative anti-fungal agents currently used in clinical therapy are ideal in terms of efficacy, anti-fungal spectrum or safety. Moreover, the rapid development of resistance to existing anti-fungal drugs has further aggravated the mortality and spread of fungi, creating an urgent need for novel anti-fungal agents. The broad spectrum of biological activities and successful usage in clinic made coumarins a promising anti-fungal candidate. Furthermore, hybridization of other pharmacophores with coumarin motif may enhance the anti-fungal efficacy, broaden the anti-fungal spectrum and improve the safety profiles. Thus, numerous coumarin hybrids have been assessed for their anti-fungal activities, and some of them showed promising potency and may have a novel mechanism of action. This review aims to outline the recent development of coumarin hybrids as potential anti-fungal agents and summarize their Structure-Activity Relationship (SAR) to provide an insight for rational designs of more active agents.


Assuntos
Antifúngicos/farmacologia , Cumarínicos/farmacologia , Fungos/efeitos dos fármacos , Antifúngicos/síntese química , Antifúngicos/química , Cumarínicos/síntese química , Cumarínicos/química , Desenho de Fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
14.
Eur J Med Chem ; 141: 335-345, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29031077

RESUMO

The emergence and wide-spread of drug-resistant bacteria including multi-drug resistant and pan-drug resistant pathogens which are associated with considerable mortality, represent a significant global health threat. 4-Quinolones which are exemplified by fluoroquinolones are the second largest chemotherapy agents used in clinical practice for the treatment of various bacterial infections. However, the resistance of bacteria to 4-quinolones develops rapidly and spreads widely throughout the world due to the long-term, inappropriate use and even abuse. To overcome the resistance and improve the potency, several strategies have been developed. Amongst them, molecular hybridization, which is based on the incorporation of two or more pharmacophores into a single molecule with a flexible linker, is one of the most practical approaches. This review aims to summarize the recent advances made towards the discovery of 4-quinolone hybrids as potential antibacterial agents as well as their structure-activity relationship (SAR). The enriched SAR may pave the way for the further rational development of 4-quinolone hybrids with excellent potency against both drug-susceptible and drug-resistant bacteria.


Assuntos
4-Quinolonas/farmacologia , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , 4-Quinolonas/síntese química , 4-Quinolonas/química , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Estrutura Molecular , Relação Estrutura-Atividade
15.
Molecules ; 22(7)2017 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-28703766

RESUMO

A series of novel 8-OMe ciprofloxacin (CPFX)-hydrazone/azole hybrids were designed, synthesized, and evaluated for their in vitro biological activities. Our results reveal that all of the hydrozone-containing hybrids (except for 7) show potency against Mycobacterium tuberculosis (MTB) H37Rv (minimum inhibitory concentration (MIC): <0.5 µM), which is better than the parent drug CPFX, and comparable to moxifloxacin and isoniazid, some of the tested Gram-positive strains (MIC: 0.06-4 µg/mL), and most Gram-negative strains (MIC: ≤0.03-4 µg/mL).


Assuntos
Ciprofloxacina/química , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/tratamento farmacológico , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antituberculosos/síntese química , Antituberculosos/química , Antituberculosos/farmacologia , Azóis/síntese química , Azóis/química , Azóis/farmacologia , Ciprofloxacina/análogos & derivados , Ciprofloxacina/síntese química , Ciprofloxacina/farmacologia , Humanos , Hidrozoários/química , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/patogenicidade , Tuberculose/microbiologia
16.
Bioorg Med Chem Lett ; 26(22): 5492-5496, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-27777007

RESUMO

A series of 12-oxime and O-oxime ether derivatives of dehydroabietic acid were synthesized and investigated for the antibacterial activity against Staphylococcus aureus Newman strain and five multidrug-resistant strains (NRS-1, NRS-70, NRS-100, NRS-108, and NRS-271). The aromatic oximate derivative 11a showed the highest activity with MIC of 0.39-0.78µg/mL against S. aureus Newman. Of note, compounds 10b, 11 and 14 showed the most potent antibacterial activity against five multidrug-resistant S. aureus with MIC values of 1.25-3.13µg/mL. These results offered useful information for further strategic optimization in search of the antibacterial candidates against infection of multidrug-resistant Gram-positive bacteria.


Assuntos
Abietanos/química , Abietanos/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Oximas/química , Oximas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Abietanos/síntese química , Antibacterianos/síntese química , Farmacorresistência Bacteriana Múltipla , Humanos , Testes de Sensibilidade Microbiana , Oximas/síntese química , Infecções Estafilocócicas/tratamento farmacológico , Relação Estrutura-Atividade
17.
Huan Jing Ke Xue ; 36(12): 4420-9, 2015 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-27011976

RESUMO

Photosynthetically active radiation (PAR) is defined as the wavelength band of 400 to 700 nm, representing most of the visible solar radiation that could be used for photosynthesis. PAR is attenuated by the absorption and scattering of nonpigment suspended matter, chromophoric dissolved organic matter and phytoplankton, and it plays an important role in determining the density and distribution of aquatic organisms. This study developed an empirical model and presented the spatial-temporal distribution of PAR diffuse attenuation coefficient [Kd (PAR)] for the slightly turbid Xin'anjiang Reservoir based on the in situ ground data and the matching Landsat 8 data. The results showed that the three-hand combinational model of Kd ( PAR) using Band 2, Band 3 and Band 8 could give a reasonable and acceptable estimation accuracy with a determination coefficient of 0. 87. Independent dataset was used to validate the model with a mean relative error of 9.16% and a root mean square error of 0.06 m⁻¹. Therefore, the three-band combination using Landsat 8 data could be used to accurately estimate Kd (PAR) in the slightly turbid Xin'anjiang Reservoir. Kd (PAR) exhibited significant seasonal and spatial differences. Kd (PAR) was higher in autumn (September-November) and summer (June-August) with the average Kd (PAR) of (0.82 ± 0.60) m⁻¹ and (0.77 ± 0.41) m⁻¹, but lower in winter (December-February) and spring (March-May) with the average Kd (PAR) of (0.56 ± 0.50) m⁻¹ and (0.40 ± 0.45 ) m⁻¹, respectively. Spatially, Kd (PAR) ranged from 0.002 to 13.86 m⁻¹ with an average of (0.64 ± 0.49) m⁻¹. The temporal heterogeneity of Kd (PAR) was mainly caused by the seasonal rainfall and seasonal growth of phytoplankton. The spatial heterogeneity was mainly caused by suspended matter concentration derived from watershed inputs and human dredging activity.


Assuntos
Fotossíntese , Imagens de Satélites , Luz Solar , China , Modelos Teóricos , Fitoplâncton , Estações do Ano , Análise Espaço-Temporal
18.
Huan Jing Ke Xue ; 35(7): 2539-46, 2014 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-25244835

RESUMO

Based on monthly in situ data collected at six sampling sites in Qiandaohu Lake between 2011 and 2012, the dynamic distributions of dissolved oxygen (DO) were analyzed and the relationships between DO and the environmental factors were investigated. The results showed that there were obviously vertical and temporal variations in the distributions of DO. In winter, the average values of DO were generally higher than those in other seasons, but no significant vertical distribution variation was found except Dabaqian. However, the vertical differences of DO in summer were larger than those in spring and autumn. Moreover, the maximum values of DO found in euphotic zone at the sites of Xiaojinshan, Santandao, Dabaqian in summer were 11.59, 12.52, 10.96 mg x L(-1), respectively. The maximum DO at surface layer was found in spring while the minimum value appeared in autumn. Seasonal differences in relationships between dissolved oxygen and water temperature, pH, and Chla concentration were discussed. In summer, highly significant linear correlation between DO and water temperature was found indicating that the temperature thermal stratification was the key factor to influence the vertical distribution of DO. The relative higher correlation coefficients between DO and pH, Chla concentration in spring and summer were due to the phytoplankton photosynthesis.


Assuntos
Monitoramento Ambiental , Lagos/química , Oxigênio/química , China , Clorofila/análise , Clorofila A , Fitoplâncton , Estações do Ano , Temperatura
19.
Acta Crystallogr C Struct Chem ; 70(Pt 2): 169-72, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24508962

RESUMO

The title organic-inorganic hybrid salts poly[trimethylsulfonium [[dichloridoantimony(III)]-di-µ-chlorido]], {(C3H9S)[SbCl4]}n, (I), and catena-poly[trimethylsulfonium [cadmium(II)-tri-µ-chlorido]], {(C3H9S)[CdCl3]}n, (II), consist of trimethylsulfonium cations and polymeric {[SbCl4](-)}n or {[CdCl3](-)}n anions. The central metal atoms are coordinated by six Cl atoms, forming an anionic {[SbCl4](-)}n three-dimensional framework (two of the four bridging chloride anions are located on two different centres of inversion) or anionic {[CdCl3](-)}n one-dimensional chains. The trimethylsulfonium cation of (II) is disordered over two sets of sites in a 0.791 (4):0.209 (4) ratio. All the anions are linked by trimethylsulfonium cations through weak C-H···Cl hydrogen bonds to form three-dimensional structures.

20.
Acta Crystallogr C ; 69(Pt 10): 1128-31, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24096500

RESUMO

The title salt, catena-poly[trimethylsulfonium [µ2-chlorido-di-µ2-thiocyanato-cadmate(II)]] {(C3H9S)[CdCl(NCS)2]}n, consists of trimethylsulfonium cations sandwiched between layers of a two-dimensional polyanion. The Cd(II) centre displays a distorted octahedral environment coordinated by two bridging Cl atoms, two thiocyanate N atoms and two thiocyanate S atoms. The thiocyanate groups adopt the µ-1,3-coordination mode and bridge the Cd(II) centres into a one-dimensional zigzag chain extended along the [110] direction. The Cd(II) centres of the zigzag chains are crosslinked by bridging Cl atoms, forming a two-dimensional polyanion. The two-dimensional anions are linked to layers of trimethylsulfonium cations by weak intermolecular C-H···Cl hydrogen bonds, forming the three-dimensional structure.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...