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1.
Bull Environ Contam Toxicol ; 104(6): 799-803, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32388572

RESUMO

Azoxystrobin (AZ), pyraclostrobin (PYR) and coumoxystrobin (COU) exert negative impacts on Chlorella vulgaris. Thus, in this study, C. vulgaris was used to assess the respiratory toxicity of AZ, PYR and COU by determining the acute toxicity, complex III activity and ATP viability. The 96 h-EC50 values of AZ, PYR and COU for C. vulgaris were 1.85, 2.21 and 1.62 mg/L, respectively. AZ, PYR and COU exerted significant effects on complex III activity and ATP viability after exposure to 0.71, 1.01 and 1.08 mg/L of the fungicides. The binding potentials of AZ, PYR and COU toward ubiquinone were - 10.44, - 9.31 and - 12.98 kcal/mol, respectively, which had adverse effects on amino acids. These results provided new insight into the potential acute respiratory toxicity mechanisms of these strobilurin fungicides in algae.


Assuntos
Acrilatos/toxicidade , Chlorella vulgaris/efeitos dos fármacos , Cumarínicos/toxicidade , Fungicidas Industriais/toxicidade , Pirimidinas/toxicidade , Estrobilurinas/toxicidade , Poluentes Químicos da Água/toxicidade , Trifosfato de Adenosina/metabolismo , Sítios de Ligação , Chlorella vulgaris/metabolismo , Relação Dose-Resposta a Droga , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Simulação de Acoplamento Molecular , Oxirredução , Testes de Toxicidade Aguda , Ubiquinona/metabolismo
2.
Zhongguo Zhong Yao Za Zhi ; 45(3): 518-522, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237508

RESUMO

Coumarin is an important class of natural organic compounds, which widely exists in a variety of plants and microorganisms. Coumarins have many biological activities and wide clinical applications, such as anti-tumor, anti-HIV, anti-bacterial, anti-inflammatory, anti-oxidation, anti-coagulation, but they have obvious toxic effects in rodents. It was found that the toxicity of coumarins in different animals and organs was significantly different, and high dose oral administration was more likely to produce toxic reactions. Based on the research and analysis of domestic and foreign literatures in recent 60 years, this paper mainly summarized the hepatotoxicity and pulmonary toxicity induced by coumarins, and probed into their possible mechanisms. It was found that the toxicity of coumarins had metabolic differences and species differences. The liver of rats and lungs of mice were more susceptible to coumarins. Toxic reactions occurred mainly in the second metabolic pathway of coumarin metabolism in vivo. In order to put forward safety considerations and evaluate the impact of coumarin on human body, it was found that coumarin is unlikely to produce hepatotoxicity at normal exposure level. It was also suggested that species differences due to different metabolic patterns in model animals should be carefully considered when assessing coumarin toxicity, in order to provide reference for clinical research and rational use of coumarins and improve the rational use of coumarins.


Assuntos
Cumarínicos/toxicidade , Animais , Humanos , Fígado/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Redes e Vias Metabólicas , Camundongos , Ratos , Especificidade da Espécie , Testes de Toxicidade
3.
J Med Chem ; 63(6): 3359-3369, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-32142286

RESUMO

Cytotoxic T-lymphocytes (CTLs) and natural killer cells (NKs) kill compromised cells to defend against tumor and viral infections. Both effector cell types use multiple strategies to induce target cell death including Fas/CD95 activation and the release of perforin and a group of lymphocyte granule serine proteases called granzymes. Granzymes have relatively broad and overlapping substrate specificities and may hydrolyze a wide range of peptidic epitopes; it is therefore challenging to identify their natural and synthetic substrates and to distinguish their localization and functions. Here, we present a specific and potent substrate, an inhibitor, and an activity-based probe of Granzyme A (GrA) that can be used to follow functional GrA in cells.


Assuntos
Cumarínicos/farmacologia , Corantes Fluorescentes/farmacologia , Granzimas/análise , Oligopeptídeos/farmacologia , Inibidores de Serino Proteinase/farmacologia , Linhagem Celular Tumoral , Cumarínicos/síntese química , Cumarínicos/toxicidade , Desenho de Fármacos , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Granzimas/química , Humanos , Oligopeptídeos/síntese química , Oligopeptídeos/toxicidade , Inibidores de Serino Proteinase/síntese química , Inibidores de Serino Proteinase/toxicidade , Especificidade por Substrato
4.
Chem Commun (Camb) ; 56(8): 1219-1222, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31895373

RESUMO

To monitor delicate changes of biological HOCl in vivo, a new probe (OH-substituted coumarin-hemicyanine, probe 2) was synthesized for NIR and ratiometric HOCl detection. Selectivity studies indicated that the electron-donating group (OH) substituted on the indolium moiety enhanced the selectivity to detect HOCl. With HOCl, the probe showed a ratiometric fluorescence (I500/I650) with a low detection limit (49.1 nM) and a rapid response (within 2 min). In addition, probe 2 was successfully applied to visualize exogenous and endogenous HOCl in living cells and animals and exhibited a perfect mitochondria target ability. This probe has been further studied as a potential and powerful tool to probe HOCl in arthritis models.


Assuntos
Cumarínicos/química , Corantes Fluorescentes/química , Ácido Hipocloroso/análise , Indóis/química , Animais , Artrite/induzido quimicamente , Artrite/diagnóstico , Carragenina , Cumarínicos/síntese química , Cumarínicos/toxicidade , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Células Hep G2 , Humanos , Indóis/síntese química , Indóis/toxicidade , Limite de Detecção , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Mitocôndrias/metabolismo , Células RAW 264.7 , Espectrometria de Fluorescência/métodos , Peixe-Zebra
5.
Anal Chim Acta ; 1094: 122-129, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31761038

RESUMO

Hypochlorite (HClO) is involved in various physiological and pathological processes as well as regulation of lysosomal functions. Thus, it is appreciated to develop efficient molecule tools for precisely detecting HClO in lysosomes. Although several lysosomal-targetable fluorogenic probes for HClO have been developed to date, they still suffered from the discounted sensing performance under lysosomal acidic condition. Herein, on the basis of the "AND" logic gate strategy, a novel dual-activatable fluorogenic probe CS has been rationally designed by simultaneously incorporating HClO recognition site and pH-sensitive group with lysosomal-targetable characteristic into a coumarin fluorophore. Different from the single-activated ones previously reported, CS exhibited good sensitivity, high specificity and fast response towards HClO under the acidic conditions but was out of operation in the neutral or alkaline environment. Importantly, it had been successfully applied for spatial-resolution imaging of exogenous or endogenous HClO in lysosomes.


Assuntos
Cumarínicos/química , Corantes Fluorescentes/química , Ácido Hipocloroso/análise , Lisossomos/metabolismo , Cumarínicos/síntese química , Cumarínicos/toxicidade , Teoria da Densidade Funcional , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Limite de Detecção , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Modelos Químicos , Espectrometria de Fluorescência/métodos
6.
Food Chem Toxicol ; 136: 111027, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31870919

RESUMO

The incubation system of CYP2E1 and CYP3A4 enzymes in rat liver microsomes was established to investigate the effects of psoralidin, isobavachalcone, neobavaisoflavone and daidzein from Fructus Psoraleae in vitro. The relevant metabolites were measured by the method of high performance liquid chromatography (HPLC), after probe substrates of 4-nitrophenol, testosterone and the drugs at different concentrations were added to the incubation systems. In addition, real-time RT-PCR was performed to determine the effect of psoralidin, neobavaisoflavone and daidzein on the mRNA expression of CYP3A4 in rat liver. The results suggested that psoralidin, isobavachalcone and neobavaisoflavone were Medium-intensity inhibitors of CYP2E1 with Ki values of 2.58, 1.28 and 19.07 µM, respectively, which could inhibit the increase of CYP2E1 and reduce diseases caused by lipid peroxidation. Isobavachalcone (Ki = 37.52 µM) showed a weak competitive inhibition on CYP3A4. Psoralidin and neobavaisoflavone showed obvious induction effects on CYP3A4 in the expression level of mRNA, which could accelerate the effects of drug metabolism and lead to the risk of inducing DDIs and serious adverse reactions. The results could be used for guideline of Fructus Psoraleae in clinic, which aimed to calculate the drug toxicity by studying the drug-drug interactions caused by the induction and inhibition of CYP450.


Assuntos
Benzofuranos/toxicidade , Chalconas/toxicidade , Cumarínicos/toxicidade , Citocromo P-450 CYP2E1/metabolismo , Citocromo P-450 CYP3A/metabolismo , Isoflavonas/toxicidade , Microssomos Hepáticos/metabolismo , Animais , Benzofuranos/metabolismo , Chalconas/metabolismo , Cumarínicos/metabolismo , Inibidores do Citocromo P-450 CYP2E1/metabolismo , Inibidores do Citocromo P-450 CYP2E1/toxicidade , Inibidores do Citocromo P-450 CYP3A/metabolismo , Inibidores do Citocromo P-450 CYP3A/toxicidade , Interações Medicamentosas , Isoflavonas/metabolismo , Ratos Sprague-Dawley
7.
BMC Pharmacol Toxicol ; 20(Suppl 1): 76, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31852548

RESUMO

BACKGROUND: Chagas disease (CD) is a tropical parasitic disease. Although the number of people infected is very high, the only drugs available to treat CD, nifurtimox (Nfx) and benznidazole, are highly toxic, particularly in the chronic stage of the disease. Coumarins are a large class of compounds that display a wide range of interesting biological properties, such as antiparasitic. Hence, the aim of this work is to find a good antitrypanosomal drug with less toxicity. The use of simple organism models has become increasingly attractive for planning and simplifying efficient drug discovery. Within these models, Caenorhabditis elegans has emerged as a convenient and versatile tool with significant advantages for the toxicological potential identification for new compounds. METHODS: Trypanocidal activity: Forty-two 4-methylamino-coumarins were assayed against the epimastigote form of Trypanosoma cruzi (Tulahuen 2 strain) by inhibitory concentration 50% (IC50). Toxicity assays: Lethal dose 50% (LD50) and Body Area were determined by Caenorhabditis elegans N2 strain (wild type) after acute exposure. Structure-activity relationship: A classificatory model was built using 3D descriptors. RESULTS: Two of these coumarins demonstrated near equipotency to Nifurtimox (IC50 = 5.0 ± 1 µM), with values of: 11 h (LaSOM 266), (IC50 = 6.4 ± 1 µM) and 11 g (LaSOM 231), (IC50 = 8.2 ± 2.3 µM). In C. elegans it was possible to observe that Nfx showed greater toxicity in both the LD50 assay and the evaluation of the development of worms. It is possible to observe that the efficacy between Nfx and the synthesized compounds (11 h and 11 g) are similar. On the other hand, the toxicity of Nfx is approximately three times higher than that of the compounds. Results from the QSAR-3D study indicate that the volume and hydrophobicity of the substituents have a significant impact on the trypanocidal activities for derivatives that cause more than 50% of inhibition. These results show that the C. elegans model is efficient for screening potentially toxic compounds. CONCLUSION: Two coumarins (11 h and 11 g) showed activity against T. cruzi epimastigote similar to Nifurtimox, however with lower toxicity in both LD50 and development of C. elegans assays. These two compounds may be a feasible starting point for the development of new trypanocidal drugs.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Cumarínicos/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Cumarínicos/síntese química , Cumarínicos/química , Cumarínicos/toxicidade , Concentração Inibidora 50 , Dose Letal Mediana , Estrutura Molecular , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade , Tripanossomicidas/síntese química , Tripanossomicidas/química , Tripanossomicidas/toxicidade , Trypanosoma cruzi/crescimento & desenvolvimento
8.
Int J Toxicol ; 38(6): 501-552, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31845612

RESUMO

Coumarin is a naturally occurring sweet-smelling benzopyrone that may be extracted from plants or synthesized for commercial uses. Its uses include as a flavoring agent, fragrance enhancer, and odor-masking additive. We reviewed and evaluated the scientific evidence on the carcinogenicity of coumarin, integrating information from carcinogenicity studies in animals with mechanistic and other relevant data, including data from toxicogenomic, genotoxicity, and metabolism studies, and studies of human variability of a key enzyme, CYP2A6. Increases in tumors were observed in multiple studies in rats and mice in multiple tissues. Our functional pathway analysis identified several common cancer-related biological processes/pathways affected by coumarin in rat liver following in vivo exposure and in human primary hepatocytes exposed in vitro. When coumarin 7-hydroxylation by CYP2A6 is compromised, this can lead to a shift in metabolism to the 3,4-epoxidation pathway and increased generation of electrophilic metabolites. Mechanistic data align with 3 key characteristics of carcinogens, namely formation of electrophilic metabolites, genotoxicity, and induction of oxidative stress. Considerations of metabolism, human variability in CYP2A6 activity, and coumarin hepatotoxicity in susceptible individuals provide additional support for carcinogenicity concern. Our analysis illustrates the importance of integrating information on human variability in the cancer hazard identification process.


Assuntos
Anticoagulantes/toxicidade , Carcinógenos/toxicidade , Cumarínicos/toxicidade , Neoplasias/induzido quimicamente , Animais , Humanos
9.
Talanta ; 205: 120095, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31450452

RESUMO

pH value is one of the most important parameters, which show significant application in environmental monitoring, chemistry and biology. Abnormal pH values always associate with some serious diseases, including cancer and Alzheimer's disease. Thus, development of highly sensitive and selective method for pH sensing and imaging is of great importance. In this paper, we synthesized a water-soluble organic probe for pH sensing either through its absorption or through its fluorescent signals. The probe was synthesized from the intermediate containing a phenol group, and the reaction was carried out in concentrated H2SO4 at 90 °C. In this way, the probe can introduce a sulfonic acid group into its structure, and thus improve its water solubility. The synthesized probe is pH-responsive, and the response process is reversible, because that the phenol group in the probe can transfer to deprotonation state with increasing the pH values to improve the intramolecular charge transfer. Meanwhile, the synthesized probe also showed high specificity and excellent biocompatibility, which is suitable for cell imaging applications.


Assuntos
Cumarínicos/química , Corantes Fluorescentes/química , Linhagem Celular Tumoral , Cumarínicos/síntese química , Cumarínicos/toxicidade , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Humanos , Concentração de Íons de Hidrogênio , Microscopia Confocal/métodos , Solubilidade , Espectrometria de Fluorescência/métodos , Espectrofotometria/métodos , Água/química
10.
Talanta ; 204: 431-437, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357316

RESUMO

Peroxynitrite anion (ONOO-), one of the reactive nitrogen species (RNS), plays momentous roles in physiological and pathological processes especially in a range of oxidative stress-related diseases. Moreover, abundant ONOO- is generated in the liver tissues of drug-induced liver injury. We report herein a novel small molecule fluorescent probe KC-ONOO for monitoring ONOO- based on boronate. The probe displayed high sensitivity and good selectivity towards ONOO-. A good linear relationship was observed between the fluorescent intensity at 530 nm and the concentration of ONOO- ranged 0-10 µM with a detection limit of 1.5 × 10-8 M. Furthermore, our probe was successfully applied for imaging ONOO- in living cells and drug-damaged liver tissues with low cytotoxicity, demonstrating the probe KC-ONOO has great potential to further elucidate more biological roles of ONOO-.


Assuntos
Benzotiazóis/química , Ácidos Borônicos/química , Cumarínicos/química , Corantes Fluorescentes/química , Ácido Peroxinitroso/análise , Animais , Benzotiazóis/síntese química , Benzotiazóis/toxicidade , Ácidos Borônicos/síntese química , Ácidos Borônicos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Cumarínicos/síntese química , Cumarínicos/toxicidade , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Células Hep G2 , Humanos , Limite de Detecção , Fígado/patologia , Masculino , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Ácido Peroxinitroso/química
11.
Talanta ; 204: 561-568, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357334

RESUMO

Cys is one of the important biothiols and its abnormal concentration may pose a threat to human health. Therefore, the monitoring of Cys in organisms is of great significance. GSH and Hcy, as the other two biothiols, have similar chemical structures and active sites to Cys. Consequently, developing fluorescent probes to independently detect Cys has become a challenging problem. Keeping this in mind, α-ß unsaturated ketone as a recognition group was integrated into the coumarin group skeleton to synthesize a fluorescent probe SC. After the nucleophilic addition reaction of Cys with SC, the conjugated system of SC was blocked and the fluorescent enhanced obviously. SC was able to detect Cys specifically under the same excitation with a low detection limit (11.1 nM). SC showed a rapid respond to Cys (120 s) and good fluorescent stability over a wide pH range. In addition, it achieved extracorporeal circulation in the presence of H2O2 or NEM. In the end, SC could be applied to detecting endogenous and exogenous Cys under biological condition due to its slight cytotoxicity and good biocompatibility. This provided a powerful tool for studying the physiological function of Cys exclusively.


Assuntos
Cumarínicos/química , Cisteína/análise , Corantes Fluorescentes/química , Cumarínicos/síntese química , Cumarínicos/toxicidade , Cisteína/química , Etilmaleimida/química , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Peróxido de Hidrogênio/química , Concentração de Íons de Hidrogênio , Limite de Detecção , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos
12.
Talanta ; 204: 868-874, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357375

RESUMO

Viscosity is a key factor that determines the diffusion-controlled processes in biological systems. The matrix of mitochondria contains various enzymes and other proteins with high density, and the diffusion of which are severely restricted by the cristae, making it the most crowded place in the cells. Herein, we reported a new near-infrared probe NV-1 with increased Stokes shift for monitoring viscosity changes in mitochondria. A remarkable increase of the fluorescence was observed in glycerol compared with which was observed in methanol at 744 nm. The probe was applied for measuring viscosity changes not only in mitochondria, but also in vivo (in zebra fishes and mice).


Assuntos
Corantes Fluorescentes/química , Mitocôndrias/metabolismo , Animais , Cumarínicos/química , Cumarínicos/efeitos da radiação , Cumarínicos/toxicidade , Feminino , Corantes Fluorescentes/efeitos da radiação , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Indóis/química , Indóis/efeitos da radiação , Indóis/toxicidade , Luz , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Mitocôndrias/química , Imagem Óptica/métodos , Viscosidade , Peixe-Zebra
13.
Analyst ; 144(15): 4687-4693, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31268078

RESUMO

Dying cell clearance is critical for myriad biological processes such as tissue homeostasis. We herein report an enzyme-activated fluorescence cell labeling approach and its use for multicolor imaging of dying cell clearance. Diacetylated 4-hydroxymandelic acid (DHA)-conjugated dyes give rise to reactive quinone methides upon deacetylation in live cells, which in turn covalently labels cellular proteins. With partner cells tagged with distinct fluorescence, apoptotic cell clearance by Raw 264.7 macrophages and epithelial HeLa cells was captured by confocal microscopy, showing the potential of DHA-based cell labeling for investigating cell-cell interactions.


Assuntos
Apoptose , Corantes Fluorescentes/química , Ácidos Mandélicos/química , Necrose , Animais , Bovinos , Linhagem Celular Tumoral , Cumarínicos/síntese química , Cumarínicos/química , Cumarínicos/toxicidade , Esterases/química , Fluoresceínas/síntese química , Fluoresceínas/química , Fluoresceínas/toxicidade , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Humanos , Ácidos Mandélicos/síntese química , Ácidos Mandélicos/toxicidade , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Estudo de Prova de Conceito , Células RAW 264.7 , Rodaminas/síntese química , Rodaminas/química , Rodaminas/toxicidade , Coloração e Rotulagem/métodos , Suínos
14.
J Environ Sci Health B ; 54(10): 866-874, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31258003

RESUMO

Mikania glomerata Sprengel, popularly known as "guaco," is used in Brazilian folk medicine for several inflammatory and allergic conditions. Besides, the popular use "guaco" is indicated by the Brazilian Ministry of Health as a safe and effective herbal medicine. The biological activity of M. glomerata extracts is due to the presence of the coumarins, a large family of phenolic substances found in plants and is made of fused benzene and α-pyrone rings. Considering that there are few data on the biological effects of the extracts of M. glomerata, mainly in genetic level, this work aims to evaluate, in vitro, the genotoxicity and coumarin production in M. glomerata in conventional and organic growing. The data showed that the organic culture system showed double the concentration of coumarin being significantly more productive than the conventional system. Besides, the results of comet assay suggest that extracts of M. glomerata cultivated in a conventional system was genotoxic, increased DNA damage levels while the organic extracts seem to have antigenotoxic effect possibly due to the concentration of coumarins. Additional biochemical investigations are necessary to elucidate the mechanisms of action of M. glomerata extracts, which were found to have a role in protection against DNA damage.


Assuntos
Agricultura/métodos , Cumarínicos/metabolismo , Mikania/metabolismo , Extratos Vegetais/toxicidade , Plantas Medicinais/metabolismo , Células Sanguíneas/citologia , Células Sanguíneas/efeitos dos fármacos , Brasil , Sobrevivência Celular/efeitos dos fármacos , Cumarínicos/toxicidade , Dano ao DNA/efeitos dos fármacos , Humanos , Mikania/química , Testes de Mutagenicidade , Agricultura Orgânica/métodos , Extratos Vegetais/análise , Extratos Vegetais/química
15.
Analyst ; 144(14): 4371-4379, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31197299

RESUMO

SO2 has been recently identified as an essential gas messenger followed by NO, CO and H2S. However, abnormal concentrations of SO2 in our bodies can cause many diseases. Thus, the real-time monitoring of SO2 to well define the generation, physiological and pathological functions of SO2 is urgently needed. In this work, we developed a novel SO2 fluorescent probe on the basis of the conjugation of semi-cyanine and coumarin derivate dyes with superior features, such as near-infrared (NIR) and two-photon dual-mode monitoring, a large Stokes shift (175 nm), ultrafast response towards SO2 (within 10 s), high selectivity and photostability. Furthermore, this probe could sense SO2 by dual colorimetric and fluorescence means. In biological imaging, the probe was able to trace exogenous and endogenous SO2 in living cells, mitochondria, E. coli, zebrafish and mice under an NIR and two-photon dual-mode. These results demonstrated that the probe has strong potential for studying the physiological and pathological functions of SO2in vitro and in vivo.


Assuntos
Cumarínicos/química , Corantes Fluorescentes/química , Indóis/química , Dióxido de Enxofre/análise , Animais , Colorimetria/métodos , Cumarínicos/síntese química , Cumarínicos/efeitos da radiação , Cumarínicos/toxicidade , Escherichia coli , Feminino , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Corantes Fluorescentes/toxicidade , Células Hep G2 , Humanos , Indóis/síntese química , Indóis/efeitos da radiação , Indóis/toxicidade , Camundongos Endogâmicos BALB C , Microscopia de Fluorescência/métodos , Imagem Óptica/métodos , Fótons , Peixe-Zebra
17.
Biomed Pharmacother ; 112: 108707, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30970513

RESUMO

The synthesis and antiproliferative effect of a series of quinoline and thiazole containing coumarin analogs 12a-d and 13a-f respectively, on mice leukemic cells was performed. The chemical structures of newly synthesized compounds were confirmed by IR, 1H NMR, 13C NMR and mass spectral analysis. The result indicates that, 7-methoxy-2-oxo-2H-chromene-3-carboxylic acid [4-(4-methoxy-phenyl)-thiazol-2-yl]-amide (13f) showed potent activity against EAC and DLA cells in MTT (15.3 µM), tryphan blue (15.6 µM) and LDH (14.2 µM) leak assay with 5-fluorouracil as a standard. Further, the anti-neoplastic effect of the compound 13f was verified against Ehrlich ascites tumour by BrdU incorporation, TUNEL, FACS and DNA fragmentation assays. Experimental data showed that compound 13f induces the apoptotic cell death by activating apoptotic factors such as caspase-8 &-3, CAD, Cleaved PARP, γ-H2AX and by degrading genomic DNA of cancer cells and thereby decreasing the ascitic tumour development in mice. Besides, compound 13f was also subjected for docking studies to approve the in vitro and in vivo studies. The data revealed that the compound 13f has very good interaction with caspase 3 protein by binding with amino acid Arg 207 through hydrogen bond.


Assuntos
Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Carcinoma de Ehrlich/tratamento farmacológico , Cumarínicos/síntese química , Quinolinas/química , Tiazóis/química , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Carcinoma de Ehrlich/patologia , Linhagem Celular Tumoral , Simulação por Computador , Cumarínicos/química , Cumarínicos/uso terapêutico , Cumarínicos/toxicidade , Dose Letal Mediana , Camundongos , Relação Estrutura-Atividade
18.
Chem Commun (Camb) ; 55(32): 4703-4706, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30942238

RESUMO

A lysosome-targeting and polarity-specific fluorescent probe CPM has been rationally designed for cancer diagnosis and imaging. We have successfully shown that lysosome polarity may serve as an ubiquitious marker for cancer detection. The potential of CPM for cancer diagnosis has also been demonstrated at the levels of live cells, organs, whole animal, and clinical patient tissue samples.


Assuntos
Cumarínicos/química , Corantes Fluorescentes/química , Lisossomos/metabolismo , Neoplasias/diagnóstico , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cumarínicos/síntese química , Cumarínicos/toxicidade , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Humanos , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos
19.
Environ Toxicol ; 34(6): 768-776, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30848542

RESUMO

Osthole (Ost) is often used in treatment for cancer, inflammation and rheumatism in clinic. However, Ost-induced liver injury has been reported. In this study, we aim to investigate the possible mechanism of Ost-induced hepatotoxicity in human normal liver cells (L02). When cells were exposed to Ost, the cell viability was decreased and apoptosis rate increased, the intracellular markers of oxidative stress were changed. Simultaneously, Ost altered apoptotic related proteins levels, including Bcl-2, Bax, Cleaved-Caspase-9/-8/-3, and Pro-Caspase-3/-8. In addition, Ost enhanced the levels of endoplasmic reticulum (ER) stress proteins (GRP78/Bip, CHOP, Caspase-4, IRE1α, PERK, JNK, P-JNK, and ATF4), decreased the cell proliferation and cycle-associated protein (Phospho-Histone H3, P-Cdc25C, Cdc25C, P-Cdc2, Cdc2, and Cyclin B1) level. The results show that Ost has toxic effects on L02 cells. Furthermore, it induces apoptosis by inhibiting cell proliferation, arresting cell cycle at the G2/M phase and activating ER stress.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cumarínicos/toxicidade , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fígado/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Técnicas de Cultura de Células , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Fígado/metabolismo , Fígado/patologia
20.
Anal Chim Acta ; 1058: 136-145, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-30851847

RESUMO

Based on conjugate addition-cyclization reaction of Cys with acrylate and subsequent 1,6-elimination of p-hydroxybenzyl moiety, a novel colorimetric and ratiometric fluorescent probe 1 was designed and synthesized. Upon addition of Cys to the solution of 1, the absorption spectra changed from 508 nm to 452 nm (Δ56 nm) and afforded visible color change from pink to yellow. Meanwhile, the emission spectra shifted from 644 nm to 539 nm (Δ105 nm) with remarkable changes in the emission ratio of F539 nm/F644 nm (R/R0 up to 760-fold), accompanying with an obvious fluorescence change from orange to green under illumination with a 365 nm UV lamp. In addition, 1 exhibited a large Stokes shift (136 nm), high sensitivity (detection limit of 46.7 nM), and excellent selectivity to Cys over Hcy and GSH. Moreover, 1 can discriminate Cys from Hcy and GSH by fluorescence spectra, even obvious visible and fluorescence color changes. Importantly, 1 can be used to image Cys in living cells by dual emission channels.


Assuntos
Acrilatos/química , Cumarínicos/química , Cisteína/análise , Corantes Fluorescentes/química , Acrilatos/síntese química , Acrilatos/toxicidade , Colorimetria/métodos , Cumarínicos/síntese química , Cumarínicos/toxicidade , Ciclização , Cisteína/química , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Limite de Detecção , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos
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