RESUMEN

Fluoride ions (F-) are one of the essential trace elements for the human body and are widely existed in nature. In this study, we present a novel fluorescent probe (YF-SZ-F) designed and synthesized for the specific detection of F-. The probe exhibits high sensitivity, excellent selectivity, and low cytotoxicity, making it a promising tool for biomedical applications. Imaging experiments conducted on zebrafish and Arabidopsis roots demonstrate the probe's remarkable cellular permeability and biocompatibility, laying a solid foundation for its potential biomedical utility. Furthermore, the probe holds potential for practical applications in environmental monitoring and public health through its capability to detect fluoride ions in water samples and via mobile phone software. This multifaceted functionality underscores the broad applicability and significance of the fluorescent probe, not only in scientific research but also in real-world scenarios, contributing to the development of more convenient and precise methods for fluoride detection.

Asunto(s)

Benzotiazoles , Colorantes Fluorescentes , Fluoruros , Pez Cebra , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Fluoruros/análisis , Animales , Benzotiazoles/química , Humanos , Arabidopsis/química , Espectrometría de Fluorescencia/métodos , Imagen Óptica

RESUMEN

BACKGROUND: In recent years, environmental pollution has been increasing due to the excessive emission of toxic ions, which has caused serious harm to human health and ecological environment. There are various methods for detecting Cu2+, S2- and Zn2+, but the traditional ion detection methods have obvious disadvantages, such as poor selectivity and long detection time. Therefore, it is still crucial to develop simple, efficient and rapid detection methods. RESULTS: A fluorescent probe based on benzothiazole, (E)-N'-(3-(benzo[d]thiazol-2-yl)-2-hydroxy-5-methylbenzylidene)-3,4,5-tris(benzyloxy)benzohydrazide (BT), was designed and synthesized. It was characterized using ESI-MS, 1H NMR, and 13C NMR. BT can be used as a chemosensor to detect Cu2+, S2- and Zn2+ in CH3CN/H2O (7:3, v/v, pH = 7.4, HEPES buffer: 0.1 M), with detection limits of 0.301 µM, 0.017 µM, and 0.535 µM, respectively. At an excitation wavelength of 320 nm, BT exhibits an "on-off-on" response to Cu2+/S2- and enhanced fluorescence response to Zn2+, with a change in fluorescence color from orange to green. The coordination ratio of ions to the probe was determined to be 1:1 through Job's plot and hydrogen spectral titration. The recognition mechanism was discussed in conjunction with theoretical calculations. Furthermore, the probe has been successfully used in test strips and medical swabs colorimetry, as well as live cell imaging. SIGNIFICANCE: The probe BT lays the foundation for the design and synthesis of multifunctional fluorescent probes. As a portable detection method, probe BT was used to detect Cu2+, S2- and Zn2+ on strips. Furthermore, the probe was applied to biological cells to detect target ions with low cytotoxicity and excellent cell permeability. This indicating that it can be used as a potential candidate for tracking Cu2+ and S2- in clinical diagnostics and biological systems.

Asunto(s)

Benzotiazoles , Cobre , Colorantes Fluorescentes , Zinc , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Benzotiazoles/química , Cobre/química , Cobre/análisis , Zinc/química , Zinc/análisis , Humanos , Imagen Óptica , Espectrometría de Fluorescencia , Células HeLa , Estructura Molecular

RESUMEN

The aggregation of amyloid ß (Aß) peptides is a significant hallmark of Alzheimer's disease (AD), and the detection of Aß aggregates and the inhibition of their formation are important for the diagnosis and treatment of AD, respectively. Herein, we report a series of benzothiazole-based Ir(III) complexes HN-1 to HN-8 that exhibit appreciable inhibition of Aß aggregation in vitro and in living cells. These Ir(III) complexes can induce a significant fluorescence increase when binding to Aß fibrils and Aß oligomers, while their measured log D values suggest these compounds could have enhanced blood-brain barrier (BBB) permeability. In vivo studies show that HN-1, HN-2, HN-3, and HN-8 successfully penetrate the BBB and stain the amyloid plaques in AD mouse brains after a 10-day treatment, suggesting that these Ir(III) complexes could act as lead compounds for AD therapeutic and diagnostic agent development.

Asunto(s)

Enfermedad de Alzheimer , Péptidos beta-Amiloides , Benzotiazoles , Complejos de Coordinación , Iridio , Agregado de Proteínas , Péptidos beta-Amiloides/antagonistas & inhibidores , Péptidos beta-Amiloides/metabolismo , Iridio/química , Iridio/farmacología , Animales , Ratones , Benzotiazoles/química , Benzotiazoles/farmacología , Humanos , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/síntesis química , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/diagnóstico , Agregado de Proteínas/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Encéfalo/metabolismo , Tiazoles

RESUMEN

Cadmium (Cd2+) is a highly toxic heavy metal that can accumulate in the human body through contaminated food and water, posing great health risks. In this study, a label-free fluorescent aptasensor based on SYBR Green I (SGI) for the rapid and sensitive detection of Cd2+ in food samples was designed. The aptasensor utilizes a Cd2+-specific aptamer (Cd-(21)) and its complementary strand (CSCd-(21)) to form a double-stranded DNA (dsDNA) structure in the absence of Cd2+. SGI intercalates into the dsDNA, resulting in a strong fluorescence signal. In the presence of Cd2+, the aptamer undergoes a conformational change, preventing the formation of dsDNA and leading to a decrease in fluorescence intensity. Under optimized conditions, the aptasensor exhibited a linear response to Cd2+ concentrations ranging from 0.11 to 157.37 ng mL-1, with a limit of detection (LOD) of 0.07 ng mL-1. The aptasensor demonstrated high specificity and was successfully applied to detect Cd2+ in fruits and vegetables, with satisfactory recovery rates (95-111%). The proposed aptasensor provides a promising tool for the rapid and sensitive detection of Cd2+ in food.

Asunto(s)

Aptámeros de Nucleótidos , Técnicas Biosensibles , Cadmio , Frutas , Límite de Detección , Verduras , Cadmio/química , Cadmio/análisis , Aptámeros de Nucleótidos/química , Verduras/química , Frutas/química , Técnicas Biosensibles/métodos , Fluorometría/métodos , Colorantes Fluorescentes/química , Contaminación de Alimentos/análisis , Benzotiazoles/química , Espectrometría de Fluorescencia/métodos , Quinolinas/química , Diaminas/química , Compuestos Orgánicos/química

RESUMEN

c-MYC is one of the most important oncogenes, which is overexpressed in many cancers, and is highly related to development, metastasis, and drug resistance of cancers. The G4 structure in the promoter of c-MYC oncogene contributes a lot to the gene transcriptional mechanism. Small-molecule ligands binding to the c-MYC G4 appear to be a new class of anticancer agents. However, selective ligands for the c-MYC G4 over other G4s have been rarely reported. In this study, we reported a novel fluorescent ligand by migrating the benzene group on a carbazole-benzothiazolium scaffold, which was demonstrated to exhibit considerable specificity to the c-MYC G4, which was distinguished from other small-molecule ligands. The further cellular experiments suggested that this ligand may indeed target the promoter G4 and cause apparent transcriptional inhibition of the c-MYC oncogene instead of other G4-mediated oncogenes, which thereby resulted in cancer cell growth inhibition. Collectively, this study provided a good example for developing specific c-MYC G4 ligands, which may further develop into an effective anticancer agent that inhibit the c-MYC expression.

Asunto(s)

Antineoplásicos , Benzotiazoles , Carbazoles , Proliferación Celular , Colorantes Fluorescentes , G-Cuádruplex , Proteínas Proto-Oncogénicas c-myc , Carbazoles/química , Carbazoles/farmacología , G-Cuádruplex/efectos de los fármacos , Humanos , Ligandos , Benzotiazoles/química , Benzotiazoles/farmacología , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-myc/genética , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/farmacología , Estructura Molecular , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Ensayos de Selección de Medicamentos Antitumorales , Relación Dosis-Respuesta a Droga , Benceno/química , Benceno/farmacología , Línea Celular Tumoral

RESUMEN

Succinate dehydrogenase (SDH) has been considered an ideal target for discovering fungicides. To develop novel SDH inhibitors, in this work, 31 novel benzothiazol-2-ylthiophenylpyrazole-4-carboxamides were designed and synthesized using active fragment exchange and a link approach as promising SDH inhibitors. The findings from the tests on antifungal activity indicated that most of the synthesized compounds displayed remarkable inhibition against the fungi tested. Compound Ig N-(2-(((5-chlorobenzo[d]thiazol-2-yl)thio)methyl)phenyl)-3-(difluoromethyl)-1-methyl-1H-yrazole-4-carboxamide, with EC50 values against four kinds of fungi tested below 10 µg/mL and against Cercospora arachidicola even below 2 µg/mL, showed superior antifungal activity than that of commercial fungicide thifluzamide, and specifically compounds Ig and Im were found to show preventative potency of 90.6% and 81.3% against Rhizoctonia solani Kühn, respectively, similar to the positive fungicide thifluzamide. The molecular simulation studies suggested that hydrophobic interactions were the main driving forces between ligands and SDH. Encouragingly, we found that compound Ig can effectively promote the wheat seedlings and the growth of Arabidopsis thaliana. Our further studies indicated that compound Ig could stimulate nitrate reductase activity in planta and increase the biomass of plants.

Asunto(s)

Inhibidores Enzimáticos , Fungicidas Industriales , Pirazoles , Succinato Deshidrogenasa , Succinato Deshidrogenasa/antagonistas & inhibidores , Succinato Deshidrogenasa/metabolismo , Fungicidas Industriales/farmacología , Fungicidas Industriales/química , Fungicidas Industriales/síntesis química , Relación Estructura-Actividad , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Pirazoles/farmacología , Pirazoles/química , Pirazoles/síntesis química , Rhizoctonia/efectos de los fármacos , Rhizoctonia/crecimiento & desarrollo , Simulación del Acoplamiento Molecular , Benzotiazoles/química , Benzotiazoles/farmacología , Proteínas Fúngicas/antagonistas & inhibidores , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/química , Ascomicetos/efectos de los fármacos , Ascomicetos/enzimología , Estructura Molecular

RESUMEN

The chromogenic reaction between 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) and ferrate [Fe(VI)] has long been utilized for Fe(VI) content measurement. However, the presence of electron-rich organic compounds has been found to significantly impact Fe(VI) detection using the ABTS method, leading to relative errors ranging from ∼88 to 100%. Reducing substances consumed ABTS•+ and resulted in underestimated Fe(VI) levels. Moreover, the oxidation of electron-rich organics containing hydroxyl groups by Fe(VI) could generate a phenoxyl radical (Ph•), promoting the transformation of Fe(VI) → Fe(V) → Fe(IV). The in situ formation of Fe(IV) can then contribute to ABTS oxidation, altering the ABTS•+:Fe(VI) stoichiometry from 1:1 to 2:1. To overcome these challenges, we introduced Mn(II) as an activator and 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic agent for Fe(VI) detection. This Mn(II)/TMB method enables rapid completion of the chromogenic reaction within 2 s, with a low detection limit of approximately 4 nM and a wide detection range (0.01-10 µM). Importantly, the Mn(II)/TMB method exhibits superior resistance to reductive interference and effectively eliminates the impact of phenoxyl-radical-mediated intermediate valence iron transfer processes associated with electron-rich organic compounds. Furthermore, this method is resilient to particle interference and demonstrates practical applicability in authentic waters.

Asunto(s)

Electrones , Oxidación-Reducción , Hierro/química , Compuestos Orgánicos/química , Benzotiazoles/química , Ácidos Sulfónicos

RESUMEN

The higher viscosity and lower pH in lysosomes of cancer cells highlight their potential as biomarkers for cancer. Therefore, the development of acid-activated viscosity fluorescent probes is significant for the early diagnosis and treatment of cancer. Based on this, we have designed and synthesized a near-infrared fluorescent probe based on the 2-(2-hydroxyphenyl)benzothiazole (HBT) group, namely HBTH, to monitor the viscosity changes within lysosomes. It has been demonstrated that HBTH was extremely sensitive to viscosity, with a strong linear relationship between fluorescence intensity and log(viscosity) within the range of (logη) = 0-3.06 (a correlation coefficient of 0.98), proving its capability for quantitative viscosity measurement. In particular, the most obvious fluorescence enhancement of HBTH was only efficiently triggered by the combined effect of low pH and high viscosity. Furthermore, HBTH can rapidly localize to lysosomes by wash-free procedure at a low concentration (100 nM) and achieve high-fidelity imaging within 20 s. It can also monitor the dynamic processes of lysosomes in cells, viscosity changes under drug stimuli, and lysosomal behavior during mitophagy. Importantly, HBTH is capable of identifying tumors in tumor-bearing nude mice through in vivo imaging. These features make HBTH a powerful tool for the early diagnosis and treatment of cancer.

Asunto(s)

Colorantes Fluorescentes , Lisosomas , Ratones Desnudos , Neoplasias , Lisosomas/metabolismo , Lisosomas/química , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Animales , Viscosidad , Humanos , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Ratones , Concentración de Iones de Hidrógeno , Línea Celular Tumoral , Benzotiazoles/química , Benzotiazoles/farmacología , Ratones Endogámicos BALB C , Imagen Óptica , Mitofagia/efectos de los fármacos

RESUMEN

Benzothiazole-bearing compounds have emerged as potential noncovalent DprE1 (decaprenylphosphoryl-ß-d-ribose-2'-epimerase) inhibitors active against Mycobacterium tuberculosis. Based on structure-based virtual screening (PDB ID: 4KW5), a focused library of thirty-one skeletally diverse benzothiazole amides was prepared, and the compounds were assessed for their antitubercular activity against M.tb H37Ra. Most potent compounds 3b and 3n were further evaluated against the M.tb H37Rv strain by the microdilution assay method. Among the compounds evaluated, bis-benzothiazole amide 3n emerged as a hit molecule and demonstrated promising antitubercular activity with minimum inhibitory concentration (MIC) values of 0.45 µg/mL and 8.0 µg/mL against H37Ra and H37Rv, respectively. Based on the preliminary hit molecule (3n), a focused library of 12 more bis-benzothiazole amide derivatives was further prepared by varying the substituents on either side to obtain new leads and generate a structure-activity relationship (SAR). Among these compounds, 6a, 6c, and 6d demonstrated remarkable antitubercular activity with MIC values of 0.5 µg/mL against H37Ra and 1.0, 2.0, and 8.0 µg/mL against H37Rv, respectively. The most active compound, 6a, also displayed significant efficacy against four drug-resistant tuberculosis strains. Compound 6a was assessed for in vitro cytotoxicity against the HepG2 cell line, and it displayed insignificant cytotoxicity. Furthermore, time-kill kinetic studies demonstrated time- and dose-dependent bactericidal activity of this compound. The GFP release assay revealed that compound 6a targets the inhibition of a cell wall component. SNPs in dprE-1 gene assessment revealed that compound 6a binds to tyrosine at position 314 of DprE1 and replaces it with histidine, causing resistance similar to that of standard TCA1. In silico docking studies further suggest that the strong noncovalent interactions of these compounds may lead to the development of potent noncovalent DprE1 inhibitors.

Asunto(s)

Antituberculosos , Proteínas Bacterianas , Benzotiazoles , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis , Antituberculosos/farmacología , Antituberculosos/química , Antituberculosos/síntesis química , Mycobacterium tuberculosis/efectos de los fármacos , Benzotiazoles/farmacología , Benzotiazoles/química , Humanos , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/metabolismo , Relación Estructura-Actividad , Simulación del Acoplamiento Molecular , Oxidorreductasas de Alcohol

RESUMEN

G-quadruplex/thioflavin T (G4/THT) is one of the ideal label-free fluorescent light-emitting elements in the field of biosensors due to its good programmability and adaptability. However, the unsatisfactory luminous efficiency of single-molecule G4/THT limits its more practical applications. Here, we developed a G4 embedded semi-catalytic hairpin assembly (G4-SCHA) reaction by rationally modifying the traditional CHA reaction, and combined with the invasive reaction, supplemented by magnetic separation technology, for label-free sensitive detection of single nucleotide polymorphisms (SNPs). The invasive reaction enabled specific recognition of single-base mutations in DNA sequences as well as preliminary signal cycle amplification. Then, magnetic separation was used to shield the false positive signals. Finally, the G4-SCHA was created for secondary amplification and label-free output of the signal. This dual-signal amplified label-free biosensor has been shown to detect mutant targets as low as 78.54 fM. What's more, this biosensor could distinguish 0.01 % of the mutant targets from a mixed sample containing a large number of wild-type targets. In addition, the detection of real and complex biological samples also verified the practical application value of this biosensor in the field of molecular design breeding. Therefore, this study improves a label-free fluorescent light-emitting element, and then proposes a simple, efficient and universal label-free SNP biosensing strategy, which also provides an important reference for the development of other G4/THT based biosensors.

Asunto(s)

Técnicas Biosensibles , G-Cuádruplex , Polimorfismo de Nucleótido Simple , Técnicas Biosensibles/métodos , Benzotiazoles/química , Humanos , ADN/química , ADN/genética , Colorantes Fluorescentes/química

RESUMEN

Mitochondrial sulfur dioxide (SO2) plays important roles in physiological and pathological activities. Unfortunately, it is lack of a reliable tool to precisely visualize the mitochondrial SO2 and elaborate its complicated functions in various cytoactivities. Here we report a mitochondrial-immobilized fluorescent probe PM-Cl consisting of coumarin and benzyl chloride modified benzothiazole, which enables selective visualization of mitochondrial SO2via chemical immobilization. The spectral results demonstrated that probe PM-Cl could respond to SO2 with high selectivity and sensitivity. Co-localization and the fluorescence of cytolysis extraction verified the excellent mitochondrial targeting and anchoring abilities. Due to the chemical immobilization, probe PM-Cl could firmly retain into mitochondria after stimulation of carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and H2O2. Significantly, a series of fluorescence images are indicative of capability for detecting the fluctuations of SO2 in mitochondria during ferroptosis. Furthermore, PM-Cl also could visualize SO2 in myocardium and muscle tissues after the stimulation of CCCP. Taken together, probe PM-Cl is a very potential molecular tool for precisely detecting mitochondrial SO2 to explore its complex functions in physiological and pathological activities.

Asunto(s)

Ferroptosis , Colorantes Fluorescentes , Mitocondrias , Dióxido de Azufre , Colorantes Fluorescentes/química , Dióxido de Azufre/análisis , Dióxido de Azufre/química , Dióxido de Azufre/metabolismo , Mitocondrias/metabolismo , Mitocondrias/química , Humanos , Animales , Ratones , Cumarinas/química , Imagen Óptica , Células HeLa , Carbonil Cianuro m-Clorofenil Hidrazona/farmacología , Benzotiazoles/química

RESUMEN

Colorectal cancer (CRC) is the third most common cancer in the world. Despite considerable improvements in the treatment of this cancer, further research to discover novel and more effective agents is ongoing. In this study, possible cytotoxic and apoptotic properties of six benzothiazolopyrimidine derivatives were studied. To assess the IC50 values of these agents, MTT assay was performed on HCT 116, CT26, and NIH/3T3 cells. Moreover, cell death mechanism induced by studied compounds was evaluated by PI/annexin V staining. Then, based on molecular docking results and in vitro experiments, the compounds with the highest anticancer properties were further analyzed in vivo in a mouse model of CRC. MTT results indicated that BTP(1) and BTP(4) had the highest selective cytotoxicity on colorectal cancer cells. Furthermore, flow cytometry results demonstrated a considerable increase in the percentage of the early apoptotic cells in BTP(1)- and BTP(4)-treated groups. In vivo studies confirmed the antitumor properties of the two compounds by a significant regression in tumor size of BTP(1)- and BTP(4)-treated mice compared to control groups. Histopathological examination of tumor tissues showed an increased number of apoptotic cells in these two groups compared to the control animals. Additionally, hematoxylin and eosin staining of the spleen and liver of treated mice did not exhibit considerable tissue damage. Thus, BTP(1) and BTP(4) can be considered promising agents in the treatment of colorectal cancer, although further experiments are required to assess their mechanism of action before their application in clinical studies.

Asunto(s)

Antineoplásicos , Apoptosis , Neoplasias del Colon , Pirimidinas , Animales , Ratones , Humanos , Pirimidinas/farmacología , Pirimidinas/química , Antineoplásicos/farmacología , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Simulación del Acoplamiento Molecular , Benzotiazoles/química , Benzotiazoles/farmacología , Células HCT116 , Células 3T3 NIH , Ratones Endogámicos BALB C , Línea Celular Tumoral

RESUMEN

A sensitive benzothiazole fluorescent probe (PBZO) for the detection of γ-glutamyl transpeptidase (GGT) activity was developed. Based on the enzymatic hydrolysis of peptide bonds by glutamyl transpeptidase, it can be specifically recognized by PBZO. The PBZO has a good linear relationship with different gradients of GGT activity at the emission wavelength of 560 nm, the Stokes shift reached 215 nm, and the detection limit of GGT activity is 0.1644 U/ml. With the increase of GGT concentration in the probe solution, the color of the solution gradually changed from orange to dark yellow under the 365 nm UV lamp. The same color change was also observed on the probe test paper. In addition, there is a linear relationship between the GGT activity and the R-value of the probe solution. More importantly, the probe has a good recovery rate in serum. Therefore, this probe can be used as a convenient tool for detecting GGT activity.

Asunto(s)

Benzotiazoles , Colorantes Fluorescentes , gamma-Glutamiltransferasa , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , gamma-Glutamiltransferasa/análisis , gamma-Glutamiltransferasa/sangre , gamma-Glutamiltransferasa/metabolismo , Benzotiazoles/química , Humanos , Espectrometría de Fluorescencia , Límite de Detección

RESUMEN

Iron-anchored nitrogen/doped carbon single-atom nanozymes (Fe-N/C), which possess homogeneous active sites and adjustable catalytic environment, represent an exemplary model for investigating the structure-function relationship and catalytic activity. However, the development of pyrolysis-free synthesis technique for Fe-N/C with adjustable enzyme-mimicking activity still presents a significant challenge. Herein, Fe-N/C anchored three carrier morphologies were created via a pyrolysis-free approach by covalent organic polymers. The peroxidase-like activity of these Fe-N/C nanozymes was regulated via the pores of the anchored carrier, resulting in varying electron transfer efficiency due to disparities in contact efficacy between substrates and catalytic sites within diverse microenvironments. Additionally, a colorimetric sensor array for identifying antioxidants was developed: (1) the Fe-N/C catalytically oxidized two substrates TMB and ABTS, respectively; (2) the development of a colorimetric sensor array utilizing oxTMB and oxABTS as sensing channels enabled accurate discrimination of antioxidants such as ascorbic acid (AsA), glutathione (GSH), cysteine (Cys), gallic acid (GA), and caffeic acid (CA). Subsequently, the sensor array underwent rigorous testing to validate its performance, including assessment of antioxidant mixtures and individual antioxidants at varying concentrations, as well as target antioxidants and interfering substances. In general, the present study offered valuable insights into the active origin and rational design of nanozyme materials, and highlighting their potential applications in food analysis.

Asunto(s)

Antioxidantes , Carbono , Colorimetría , Hierro , Nitrógeno , Colorimetría/métodos , Antioxidantes/análisis , Antioxidantes/química , Nitrógeno/química , Hierro/química , Hierro/análisis , Carbono/química , Ácido Gálico/química , Ácido Gálico/análisis , Catálisis , Bencidinas/química , Ácido Ascórbico/análisis , Ácido Ascórbico/química , Nanoestructuras/química , Benzotiazoles/química , Glutatión/análisis , Glutatión/química , Ácidos Cafeicos/análisis , Ácidos Cafeicos/química , Cisteína/análisis , Cisteína/química , Ácidos Sulfónicos/química , Oxidación-Reducción

RESUMEN

In this study, we developed an isothermal fluorometric diagnostic method for DNA virus-generating disorders such as Mpox. Our results showed that the release of a large number of protons during multiplex-LAMP markedly lowered the pH level, which transformed the retinoblastoma (Rb) linear ssDNA into i-motifs. Consequently, thiazole orange (TO; a fluorometric probe sensitive to the i-motif) boosted the signal-on fluorescence because of its ability to bind selectively to i-motifs. This multiplex-LAMP/i-motif-TO system enabled simultaneous detection aimed at numerous potential targets with remarkable sensitivity (1.47 pg per mL) and efficiency (30 minutes). Our method is expected to enable DNA-virus-related diseases to be efficiently and accurately assessed.

Asunto(s)

Benzotiazoles , Fluorometría , Fluorometría/métodos , Benzotiazoles/química , Quinolinas/química , Colorantes Fluorescentes/química , Técnicas de Amplificación de Ácido Nucleico/métodos , ADN Viral/análisis , Concentración de Iones de Hidrógeno , ADN de Cadena Simple/química , Motivos de Nucleótidos

RESUMEN

RNA G4, as an integral branch of G4 structure, possesses distinct interactions with ligands compared to the common DNA G4, thus the investigation of RNA G4/ligand interactions might be considered as a fresh breakthrough to improve the biosensing performance of G4/ligand system. In this study, we comparatively explored the structural and functional mechanisms of RNA G4 and DNA G4 in the interaction with ligands, hemin and thioflavin T (ThT), utilizing the classical PS2.M sequence as a model. We found that although the catalytic performance of RNA G4/hemin system was lower than DNA G4/hemin, RNA G4/ThT fluorescence system exhibited a significant improvement (2∼3-fold) compared to DNA G4/ThT, and adenine modification could further enhance the signaling. Further, by exploring the interaction between RNA G4 and ThT, we deemed that RNA G4 and ThT were stacked in a bimolecular mode compared to single-molecule binding of DNA G4/ThT, thus more strongly limiting the structural spin in ThT excited state. Further, RNA G4/ThT displayed higher environmental tolerance and lower ion dependence than DNA G4/ThT. Finally, we employed RNA G4/ThT as a highly sensitive label-free fluorescent signal output system for in situ imaging of isoforms BCR-ABL e13a2 and e14a2. Overall, this study successfully screened a high-performance RNA G4 biosensing system through systematic RNA G4/ligands interaction studies, which was expected to provide a promising reference for subsequent G4/ligand research.

Asunto(s)

Benzotiazoles , G-Cuádruplex , ARN , Ligandos , ARN/química , ARN/metabolismo , Benzotiazoles/química , Humanos , Hemina/química , Hemina/metabolismo

RESUMEN

In this review, we present a systematic and comprehensive summary of the recent developments in the synthetic strategies of 2-(2-hydroxyarylsubstituted)-benzothiazole (HBT) framework along with incorporation of various substituents on phenolic and benzothiazole rings which affect the emission process. The literature, spanning the years 2015-2024, on excited-state intramolecular proton transfer (ESIPT)-based studies of HBT derivatives comprising the effects of solvent polarity, substituents, and extended conjugation on fluorophores has been searched. ESIPT, intramolecular charge transfer, and aggregation-induced emissions enable these fluorescent probes to specifically interact with analytes, thereby altering their luminescence characteristics to achieve analyte detection. These fluorescent probes exhibit large Stokes shifts, high quantum yields, and excellent color transitions. Finally, the applications of HBTs as ESIPT-based fluorescent probes for the detection of cations, anions, and biomolecules have been summarized. We anticipate that this review will provide a comprehensive overview of the current state of research in this field and encourage researchers to develop novel ESIPT-based fluorophores with new applications.

Asunto(s)

Benzotiazoles , Colorantes Fluorescentes , Protones , Benzotiazoles/química , Benzotiazoles/síntesis química , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Iones/química , Iones/análisis , Estructura Molecular

RESUMEN

Leishmaniasis is a disease caused by protozoa Leishmania spp., considered as a significant and urgent public health problem mainly in developing countries. In the absence of an effective vaccine, the treatment of infected people is one of the most commonly prophylactic measures used to control this disease. However, the therapeutic arsenal is reduced to a few drugs, with serious side effects and variability in efficacy. Attempting to this problem, in this work, a series of benzothiazole derivatives was synthetized and assayed against promastigotes and intracellular amastigotes of L. amazonensis, as well as the toxicity on macrophages. In addition, studies about the mechanism of action were also performed. Among the synthesized molecules, the substitution at position 4 of the aromatic ring appears to be critical for activity. The best compound exhibited IC50 values of 28.86 and 7.70 µM, against promastigotes and amastigotes of L. amazonensis, respectively, being more active than miltefosine, used as reference drug. The in silico analysis of physicochemical and pharmacokinetic (ADMET) properties of this compound suggested a good profile of oral bioavailability and safety. In conclusion, the strategy of using benzothiazole nucleous in the search for new antileishmanial agents was advantageous and preliminar data provide information about the mechanism of action as well as in silico parameters suggest a good profile for preclinical studies.

Asunto(s)

Antiprotozoarios , Benzotiazoles , Hidrazonas , Leishmania , Benzotiazoles/química , Benzotiazoles/farmacología , Benzotiazoles/síntesis química , Antiprotozoarios/farmacología , Antiprotozoarios/química , Antiprotozoarios/síntesis química , Animales , Hidrazonas/química , Hidrazonas/farmacología , Hidrazonas/síntesis química , Ratones , Leishmania/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/parasitología , Relación Estructura-Actividad , Humanos

RESUMEN

Benzothiazole compounds are known as an important bicyclic ring system with multiple applications. These compounds have a wide range of biological activities, including anticancer, antimicrobial, anti-inflammatory and antiviral activities. In this study, benzothiazole compounds were synthesized and their various biological activities were examined. The synthesized benzothiazoles were evaluated for their antimicrobial properties against various bacterial and fungal strains. The compound 6e is most active ligand in the series against bacteria and fungi as compared to standard antibiotics. Especially, this compound significant effect against Staphylococcus aureus (32.00 ± 1.73 mm). These compounds exhibited potent anticancer activity against gastrointestinal cancer cells, demonstrating their potential as therapeutic agents. The lowest antiproliferative response after administration of the compounds was observed in HCT116 cells, while the most effective antiproliferative response was observed in AGS cells (> 10 µg/mL). In all cell lines, 40 and 100 µg/mL application values of the selected compounds showed significant increases in the expression of caspase-3, 8 and 9. We also utilized a computational docking approach to investigate the interaction of these benzothiazoles with VEGFR-2 kinase. Our docking studies showed that compounds 6a and 6d may be promising therapeutic agents against gastrointestinal system cancers due to their ability to bind to VEGFR-2 kinase.

Asunto(s)

Antineoplásicos , Benzotiazoles , Microondas , Simulación del Acoplamiento Molecular , Humanos , Benzotiazoles/farmacología , Benzotiazoles/síntesis química , Benzotiazoles/química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Pruebas de Sensibilidad Microbiana , Tecnología Química Verde , Proliferación Celular/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antiinfecciosos/farmacología , Antiinfecciosos/síntesis química

RESUMEN

Compounds with sulfhydryl substituents and azole compounds exhibit potent anti-tyrosinase potency. 2-Thiobenzothiazole (2-TBT), a hybrid structure of sulfhydryl and azole, exists in two tautomeric forms, with the thione form being predominant according to several studies. 2-TBT derivatives were synthesized as potential tyrosinase inhibitors as the thione tautomeric form has the same N-CS moiety as phenylthiourea (PTU), which is suitable for chelation with the copper ions present in the tyrosinase active site. Eight of the ten 2-TBT derivatives inhibited the monophenolase and diphenolase activities of mushroom tyrosinase, with IC50 values of 0.02-0.83 µM. Kinetic studies and molecular dynamics simulations were performed to determine their mode of action and confirm that the 2-TBT derivatives bind to the tyrosinase active site with high stability. Derivatives 3, 4, 8, and 10 strongly inhibited melanogenesis in B16F10 cells in a pattern similar to the results of cellular tyrosinase inhibition, thereby suggesting that their ability to inhibit melanogenesis was due to their tyrosinase inhibitory activity. In a depigmentation experiment using zebrafish embryos, all 2-TBT derivatives showed better potency than kojic acid, even at 400 to 2000 times lower concentration, and 1 and 10 reduced zebrafish larva pigmentation more strongly than PTU even at 20 times lower concentration. Experiments investigating the changes in tyrosinase inhibitory activity of 2-TBT derivatives in the presence and absence of CuSO4 and their copper chelating ability supported that these derivatives exert their anti-melanogenic effect by chelating the copper ions of tyrosinase. These results suggest that 2-TBT derivatives are promising candidates for the treatment of hyperpigmentation-related disorders.

Asunto(s)

Benzotiazoles , Inhibidores Enzimáticos , Melaninas , Monofenol Monooxigenasa , Pez Cebra , Animales , Ratones , Agaricales/enzimología , Benzotiazoles/farmacología , Benzotiazoles/química , Benzotiazoles/síntesis química , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Melaninas/antagonistas & inhibidores , Melaninas/metabolismo , Estructura Molecular , Monofenol Monooxigenasa/antagonistas & inhibidores , Monofenol Monooxigenasa/metabolismo , Feniltiourea/química , Feniltiourea/farmacología , Relación Estructura-Actividad