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1.
Anal Chem ; 96(15): 5931-5939, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38573171

RESUMEN

Cuproptosis is a novel copper-dependent form of programmed cell death, displaying important regulatory functions in many human diseases, including cancer. However, the relationship between the changes in mitochondrial viscosity, a key factor associated with cellular malfunction, and cuproptosis is still unclear. Herein, we prepared a phosphorescent iridium (Ir) complex probe for precisely monitoring the changes of mitochondrial viscosity during cuprotosis via phosphorescence lifetime imaging. The Ir complex probe possessed microsecond lifetimes (up to 1 µs), which could be easily distinguished from cellular autofluorescence to improve the imaging contrast and sensitivity. Benefiting from the long phosphorescence lifetime, excellent viscosity selectivity, and mitochondrial targeting abilities, the Ir complex probe could monitor the increase in the mitochondrial viscosity during cuproptosis (from 46.8 to 68.9 cP) in a quantitative manner. Moreover, through in situ fluorescence imaging, the Ir complex probe successfully monitored the increase in viscosity in zebrafish treated with lipopolysaccharides or elescolomol-Cu2+, which were well-known cuproptosis inducers. We anticipate that this new Ir complex probe will be a useful tool for in-depth understanding of the biological effects of mitochondrial viscosity during cuproptosis.


Asunto(s)
Iridio , Pez Cebra , Animales , Humanos , Viscosidad , Pez Cebra/metabolismo , Línea Celular Tumoral , Células HeLa
2.
Anal Chem ; 95(9): 4390-4394, 2023 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-36802493

RESUMEN

Chemical nerve agents are highly toxic organophosphorus compounds that are easy to obtain and can be utilized by terrorists to threaten homeland security and human safety. Those organophosphorus nerve agents contain nucleophilic ability that can react with acetylcholinesterase leading to muscular paralysis and human death. Therefore, there is great importance to explore a reliable and simple method to detect chemical nerve agents. Herein, the o-phenylenediamine-linked dansyl chloride as a colorimetric and fluorescent probe has been prepared to detect specific chemical nerve agent stimulants in the solution and vapor phase. The o-phenylenediamine unit serves as a detection site that can react with diethyl chlorophosphate (DCP) in a rapid response within 2 min. A satisfied relationship line was obtained between fluorescent intensity and the concentration of DCP in the range of 0-90 µM. In the optimized conditions, we conducted the fluorescent titration to measure the limits of detection (0.082 µM) with the fluorescent enhancement up to 18-fold. Fluorescence titration and NMR studies were also conducted to explore the detection mechanism, indicating that the formation of phosphate ester causes the intensity of fluorescent change during the PET process. Finally, probe 1 coated with the paper test is utilized to detect DCP vapor and solution by the naked eye. We expect that this probe may give some admiration to design the small molecule organic probe and applied in the selectivity detection of chemical nerve agents.


Asunto(s)
Estimulantes del Sistema Nervioso Central , Agentes Nerviosos , Humanos , Agentes Nerviosos/química , Colorantes Fluorescentes/química , Acetilcolinesterasa , Gases
3.
Mar Drugs ; 21(2)2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36827144

RESUMEN

Based on the structures of natural products streptochlorin and pimprinine derived from marine or soil microorganisms, a series of streptochlorin derivatives containing the nitrile group were designed and synthesized through acylation and oxidative annulation. Evaluation for antifungal activity showed that compound 3a could be regarded as the most promising candidate-it demonstrated over 85% growth inhibition against Botrytis cinerea, Gibberella zeae, and Colletotrichum lagenarium, as well as a broad antifungal spectrum in primary screening at the concentration of 50 µg/mL. The SAR study revealed that non-substituent or alkyl substituent at the 2-position of oxazole ring were favorable for antifungal activity, while aryl and monosubstituted aryl were detrimental to activity. Molecular docking models indicated that 3a formed hydrogen bonds and hydrophobic interactions with Leucyl-tRNA Synthetase, offering a perspective for the possible mechanism of action for antifungal activity of the target compounds.


Asunto(s)
Antifúngicos , Fungicidas Industriales , Antifúngicos/farmacología , Estructura Molecular , Relación Estructura-Actividad , Simulación del Acoplamiento Molecular , Oxazoles/química , Fungicidas Industriales/farmacología
4.
Bioorg Med Chem ; 35: 116073, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33610010

RESUMEN

Streptochlorin is a small molecule of indole alkaloid isolated from marine Streptomyces sp., it is a promising lead compound due to its potent bioactivity in preventing many phytopathogens in our previous study, but further structural modifications are required to improve its antifungal activity. Our work in this paper focused on the replacement of oxazole ring in streptochlorin with the imidazole ring, to discover novel analogues. Based on this design strategy, three series of streptochlorin analogues were efficiently synthesized through sequential Vilsmeier-Haack reaction, Van Leusen imidazole synthesis and halogenation reaction. Some of the analogues displayed excellent activity in the primary assays, and this is highlighted by compounds 4g and 4i, the growth inhibition against Alternaria Leaf Spot and Rhizoctorzia solani under 50 µg/mL are 97.5% and 90.3%, respectively, even more active than those of streptochlorin, pimprinine and Osthole. Molecular docking models indicated that streptochlorin binds with Thermus thermophiles Leucyl-tRNA Synthetase in a similar mode to AN2690, offering a perspective on the mode of action study for antifungal activities of streptochlorin derivatives. Further study is still ongoing with the aim of discovering synthetic analogues, with improved antifungal activity and clear mode of action.


Asunto(s)
Alternaria/efectos de los fármacos , Antifúngicos/farmacología , Diseño de Fármacos , Indoles/farmacología , Simulación del Acoplamiento Molecular , Oxazoles/farmacología , Rhizoctonia/efectos de los fármacos , Antifúngicos/síntesis química , Antifúngicos/química , Relación Dosis-Respuesta a Droga , Indoles/síntesis química , Indoles/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Oxazoles/síntesis química , Oxazoles/química , Relación Estructura-Actividad
5.
Mol Divers ; 25(1): 205-221, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32056130

RESUMEN

Based on the strategy of diversity-oriented synthesis and the structures of natural product pimprinine and streptochlorin, two series of novel pimprinine derivatives containing 1,3,4-oxadiazole-5-thioether moieties were efficiently synthesized under the optimized reaction conditions. Biological assays conducted at Syngenta showed the designed derivatives displayed an altered pattern of biological activity, of which 5h was identified as the most promising compound with strong activity against Pythium dissimile and also a broad antifungal spectrum in primary screening. Further structural optimization of pimprinine and streptochlorin derivatives is well under way, aiming to discover synthetic analogues with improved antifungal activity. Two series of novel pimprinine derivatives containing 1,3,4-oxadiazole-5-thioether moieties were efficiently synthesized through diversity-oriented synthesis strategy under the optimized conditions. Biological assays showed the designed derivatives exhibited potential activity.


Asunto(s)
Antifúngicos/síntesis química , Oxadiazoles/química , Oxazoles/química , Sulfuros/química , Antifúngicos/química , Antifúngicos/farmacología , Productos Biológicos/química , Productos Biológicos/farmacología , Indoles/química , Pruebas de Sensibilidad Microbiana/métodos , Pythium/efectos de los fármacos , Relación Estructura-Actividad
6.
Bioorg Med Chem ; 28(18): 115624, 2020 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-32828433

RESUMEN

Fructose-1,6-bisphosphatase (FBPase) is an attractive target for affecting the GNG pathway. In our previous study, the C128 site of FBPase has been identified as a new allosteric site, where several nitrovinyl compounds can bind to inhibit FBPase activity. Herein, a series of nitrostyrene derivatives were further synthesized, and their inhibitory activities against FBPase were investigated in vitro. Most of the prepared nitrostyrene compounds exhibit potent FBPase inhibition (IC50 < 10 µM). Specifically, when the substituents of F, Cl, OCH3, CF3, OH, COOH, or 2-nitrovinyl were installed at the R2 (meta-) position of the benzene ring, the FBPase inhibitory activities of the resulting compounds increased 4.5-55 folds compared to those compounds with the same groups at the R1 (para-) position. In addition, the preferred substituents at the R3 position were Cl or Br, thus compound HS36 exhibited the most potent inhibitory activity (IC50 = 0.15 µM). The molecular docking and site-directed mutation suggest that C128 and N125 are essential for the binding of HS36 and FBPase, which is consistent with the C128-N125-S123 allosteric inhibition mechanism. The reaction enthalpy calculations show that the order of the reactions of compounds with thiol groups at the R3 position is Cl > H > CH3. CoMSIA analysis is consistent with our proposed binding mode. The effect of compounds HS12 and HS36 on glucose production in primary mouse hepatocytes were further evaluated, showing that the inhibition was 71% and 41% at 100 µM, respectively.


Asunto(s)
Inhibidores Enzimáticos/química , Fructosa-Bifosfatasa/antagonistas & inhibidores , Estirenos/química , Sitio Alostérico , Secuencia de Aminoácidos , Animales , Diseño de Fármacos , Inhibidores Enzimáticos/metabolismo , Gluconeogénesis , Glucosa/metabolismo , Hepatocitos/citología , Hepatocitos/metabolismo , Humanos , Isomerismo , Cinética , Ratones , Simulación del Acoplamiento Molecular , Unión Proteica , Relación Estructura-Actividad , Estirenos/metabolismo
7.
Angew Chem Int Ed Engl ; 59(37): 16154-16160, 2020 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-32573047

RESUMEN

Understanding the biomolecular interactions in a specific organelle has been a long-standing challenge because it requires super-resolution imaging to resolve the spatial locations and dynamic interactions of multiple biomacromolecules. Two key difficulties are the scarcity of suitable probes for super-resolution nanoscopy and the complications that arise from the use of multiple probes. Herein, we report a quinolinium derivative probe that is selectively enriched in mitochondria and switches on in three different fluorescence modes in response to hydrogen peroxide (H2 O2 ), proteins, and nucleic acids, enabling the visualization of mitochondrial nucleoprotein dynamics. STED nanoscopy reveals that the proteins localize at mitochondrial cristae and largely fuse with nucleic acids to form nucleoproteins, whereas increasing H2 O2 level leads to disassociation of nucleic acid-protein complexes.


Asunto(s)
Colorantes Fluorescentes/química , Mitocondrias/metabolismo , Proteínas Nucleares/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Células Hep G2 , Humanos , Peróxido de Hidrógeno/metabolismo , Ácidos Nucleicos/metabolismo
8.
Exp Cell Res ; 369(2): 226-233, 2018 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-29802837

RESUMEN

Human embryonic stem cells (hESCs) are highly fragile with massive cell death after dissociation into single cells, which seriously hampers their applications. The mechanism underlying the massive cell death after dissociation still remains elusive. Here, the expression of apoptosis-related proteins, cell survival and mitochondrial membrane potential in dissociated hESCs before and after the treatments with a protein kinase A (PKA) inhibitor H89 and p53 inhibitor Pifithrin α were investigated, respectively. Protein interactions were identified by immunoprecipitation and immunofluorescence. The results show that the dissociation causes Caspase-dependent apoptosis in hESCs mediated by mitochondrial pathway with the up-regulation of pro-apoptotic proteins, decrease in mitochondrial membrane potential and elevation in pro-apoptotic Cyto c release, which are obviously suppresses by H89. The dissociation-induced increase of phosphorylated p53 Ser15 (p-p53) is suppressed by Pifithrin α which also rescues the elevated levels of pro-apoptotic proteins in mitochondrial pathway. During the dissociation-induced apoptosis, PKA/p-p53/Bax signaling pathway is identified by immunoprecipitation and immunofluorescence showing the most likely interaction between them. These results indicate that dissociation induces mitochondrial apoptosis in hESCs involving PKA/p-p53/Bax signaling pathway, which not only give new insights into the apoptosis mechanism of dissociated hESCs, but also provide clues for developing potential strategies to promote hESC survival after dissociation.


Asunto(s)
Apoptosis/fisiología , Células Madre Embrionarias Humanas/citología , Células Madre Embrionarias Humanas/metabolismo , Mitocondrias/metabolismo , Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Células Madre Embrionarias Humanas/efectos de los fármacos , Humanos , Isoquinolinas/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Transducción de Señal/fisiología , Sulfonamidas/farmacología , Proteína p53 Supresora de Tumor/química , Proteína p53 Supresora de Tumor/metabolismo , Proteína X Asociada a bcl-2/metabolismo
9.
J Chem Inf Model ; 57(6): 1426-1438, 2017 06 26.
Artículo en Inglés | MEDLINE | ID: mdl-28475320

RESUMEN

Class II fructose-1,6-bisphosphate aldolases (FBA-II) are attractive new targets for the discovery of drugs to combat invasive fungal infection, because they are absent in animals and higher plants. Although several FBA-II inhibitors have been reported, none of these inhibitors exhibit antifungal effect so far. In this study, several novel inhibitors of FBA-II from C. albicans (Ca-FBA-II) with potent antifungal effects were rationally designed by jointly using a specific protocols of molecular docking-based virtual screening, accurate binding-conformation evaluation strategy, synthesis and enzymatic assays. The enzymatic assays reveal that the compounds 3c, 3e-g, 3j and 3k exhibit high inhibitory activity against Ca-FBA-II (IC50 < 10 µM), and the most potential inhibitor is 3g, with IC50 value of 2.7 µM. Importantly, the compounds 3f, 3g, and 3l possess not only high inhibitions against Ca-FBA-II, but also moderate antifungal activities against C. glabrata (MIC80 = 4-64 µg/mL). The compounds 3g, 3l, and 3k in combination with fluconazole (8 µg/mL) displayed significantly synergistic antifungal activities (MIC80 < 0.0625 µg/mL) against resistant Candida strains, which are resistant to azoles drugs. The probable binding modes between 3g and the active site of Ca-FBA-II have been proposed by using the DOX (docking, ONIOM, and XO) strategy. To our knowledge, no FBA-II inhibitors with antifungal activities against wild type and resistant strains from Candida were reported previously. The positive results suggest that the strategy adopted in this study are a promising method for the discovery of novel drugs against azole-resistant fungal pathogens in the future.


Asunto(s)
Antifúngicos/química , Antifúngicos/farmacología , Candida albicans/enzimología , Diseño de Fármacos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Fructosa-Bifosfato Aldolasa/antagonistas & inhibidores , Candida albicans/efectos de los fármacos , Fructosa-Bifosfato Aldolasa/química , Fructosa-Bifosfato Aldolasa/metabolismo , Fructosadifosfatos/metabolismo , Pruebas de Sensibilidad Microbiana , Simulación de Dinámica Molecular
10.
J Chem Inf Model ; 56(1): 73-81, 2016 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-26669534

RESUMEN

In the present study, a series of novel maleimide derivatives were rationally designed and optimized, and their inhibitory activities against cyanobacteria class-II fructose-1,6-bisphosphate aldolase (Cy-FBA-II) and Synechocystis sp. PCC 6803 were further evaluated. The experimental results showed that the introduction of a bigger group (Br, Cl, CH3, or C6H3-o-F) on the pyrrole-2',5'-dione ring resulted in a decrease in the Cy-FBA-II inhibitory activity of the hit compounds. Generally, most of the hit compounds with high Cy-FBA-II inhibitory activities could also exhibit high in vivo activities against Synechocystis sp. PCC 6803. Especially, compound 10 not only shows a high Cy-FBA-II activity (IC50 = 1.7 µM) but also has the highest in vivo activity against Synechocystis sp. PCC 6803 (EC50 = 0.6 ppm). Thus, compound 10 was selected as a representative molecule, and its probable interactions with the surrounding important residues in the active site of Cy-FBA-II were elucidated by the joint use of molecular docking, molecular dynamics simulations, ONIOM calculations, and enzymatic assays to provide new insight into the binding mode of the inhibitors and Cy-FBA-II. The positive results indicate that the design strategy used in the present study is very likely to be a promising way to find novel lead compounds with high inhibitory activities against Cy-FBA-II in the future. The enzymatic and algal inhibition assays suggest that Cy-FBA-II is very likely to be a promising target for the design, synthesis, and development of novel specific algicides to solve cyanobacterial harmful algal blooms.


Asunto(s)
Diseño de Fármacos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Fructosa-Bifosfato Aldolasa/antagonistas & inhibidores , Relación Estructura-Actividad Cuantitativa , Synechocystis/enzimología , Dominio Catalítico , Técnicas de Química Sintética , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/metabolismo , Fructosa-Bifosfato Aldolasa/química , Fructosa-Bifosfato Aldolasa/metabolismo , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Pirroles/síntesis química , Pirroles/química , Pirroles/metabolismo , Pirroles/farmacología
11.
Bioorg Med Chem ; 24(6): 1225-30, 2016 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-26860927

RESUMEN

1,3,8-Trihydroxynaphthalene reductase (3HNR) is an essential enzymes that is involved in fungal melanin biosynthesis. Based on the structural informations of active site of 3HNR, a series of ß-nitrostyrene compounds were rationally designed and synthesized. The enzymatic activities of these compounds showed that most of them exhibited high inhibitory activities (<5.0 µM) against 3HNR; compound 3-2 exhibit the highest inhibitory activity (IC50=0.29 µM). In particular, some of these compounds had moderate fungicidal activity against Magnaporthe grisea. Compound 3-4 showed high in vivo activities against M. grisea (EC50=9.5 ppm). Furthermore, compound 3-2 was selected as a representative molecule, and the probable binding mode of this compound and the surrounding residues in the active site of 3HNR was elucidated by using molecular dock. The positive results suggest that ß-nitrostyrene derivatives are most likely to be promising leads toward the discovery of novel agent of rice blast.


Asunto(s)
Antifúngicos/farmacología , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Proteínas Fúngicas/antagonistas & inhibidores , Magnaporthe/efectos de los fármacos , Magnaporthe/enzimología , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/antagonistas & inhibidores , Estirenos/farmacología , Antifúngicos/síntesis química , Antifúngicos/química , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Proteínas Fúngicas/metabolismo , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/metabolismo , Relación Estructura-Actividad , Estirenos/síntesis química , Estirenos/química
12.
J Comput Chem ; 36(3): 137-45, 2015 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-25363207

RESUMEN

Within the framework of the Förster theory, the electronic excitation energy transfer pathways in the cyanobacteria allophycocyanin (APC) trimer and hexamer were studied. The associated physical quantities (i.e., excitation energy, oscillator strength, and transition dipole moments) of the phycocyanobilins (PCBs) located in APC were calculated at time-dependent density functional theory (TDDFT) level of theory. To estimate the influence of protein environment on the preceding calculated physical quantities, the long-range interactions were approximately considered with the polarizable continuum model at the TDDFT level of theory, and the short-range interaction caused by surrounding aspartate residue of PCBs were taken into account as well. The shortest energy transfer time calculated in the framework of the Förster model at TDDFT/B3LYP/6-31+G* level of theory are about 0.10 ps in the APC trimer and about 170 ps in the APC monomer, which are in qualitative agreement with the experimental finding that a very fast lifetime of 0.43-0.44 ps in APC trimers, whereas its monomers lacked any corresponding lifetime. These results suggest that the lifetime of 0.43-0.44 ps in the APC trimers determined by Sharkov et al. was most likely attributed to the energy transfer of α(1) -84 ↔ ß(3) -84 (0.23 ps), ß(1) -84 ↔ α(2) -84 (0.11 ps) or ß(2) -84 ↔ α(3) -84 (0.10 ps). So far, no experimental or theoretical energy transfer rates between two APC trimmers were reported, our calculations predict that the predominate energy transfer pathway between APC trimers is likely to occur from α(3) -84 in one trimer to α(5) -84 in an adjacent trimer with a rate of 32.51 ps.


Asunto(s)
Biopolímeros/química , Cianobacterias/química , Transferencia Resonante de Energía de Fluorescencia , Ficocianina/química , Electrones , Modelos Moleculares
13.
J Phys Chem B ; 128(24): 5846-5854, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38830814

RESUMEN

Hydrogen sulfide (H2S) is an important endogenous gas transmitter that plays a critical role in various physiological and pathological processes and can also cause a negative impact on foodstuffs. In this study, we designed and synthesized a simple, easily available, high-yield, and low-cost near-infrared (λem = 710 nm) fluorescent probe, DEM-H2S, with a substantial Stokes shift (205 nm) for the detection of H2S. DEM-H2S features high selectivity and sensitivity (LOD = 80 nM) toward H2S, accompanied by a noticeable color change. Upon interaction with H2S, DEM-H2S exhibits a restored ICT (Intramolecular Charge Transfer) process, thereby manifesting near-infrared fluorescence. DEM-H2S has been successfully utilized to detect H2S in actual water samples and to monitor the spoilage of food items, such as pork, shrimp, and eggs. Furthermore, DEM-H2S enables the imaging of endogenous and exogenous H2S in living MCF-7 cells and zebrafish. Hence, DEM-H2S provides an attractive method for the detection of H2S in environmental, food, and biological systems, holding potential value in physiological and pathological research.


Asunto(s)
Colorantes Fluorescentes , Sulfuro de Hidrógeno , Pez Cebra , Sulfuro de Hidrógeno/análisis , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Humanos , Animales , Células MCF-7 , Agua/química , Imagen Óptica , Contaminación de Alimentos/análisis , Límite de Detección , Huevos/análisis , Espectrometría de Fluorescencia , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/química
14.
J Comput Chem ; 34(12): 1005-12, 2013 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-23299487

RESUMEN

In the present study, the electronic energy transfer pathways in trimeric and hexameric aggregation state of cyanobacteria C-phycocyanin (C-PC) were investigated in term of the Förster theory. The corresponding excited states and transition dipole moments of phycocyanobilins (PCBs) located into C-PC were examined by model chemistry in gas phase at time-dependent density functional theory (TDDFT), configuration interaction-singles (CIS), and Zerner's intermediate neglect of differential overlap (ZINDO) levels, respectively. Then, the long-range pigment-protein interactions were approximately taken into account by using polarizable continuum model (PCM) at TDDFT level to estimate the influence of protein environment on the preceding calculated physical quantities. The influence of the short-range interaction caused by aspartate residue nearby PCBs was examined as well. Only when the protonation of PCBs and its long- and short-range interactions were properly taken into account, the calculated energy transfer rates (1/K) in the framework of Förster model at TDDFT/B3LYP/6-31+G* level were in good agreement with the experimental results of C-PC monomer and trimer. Furthermore, the present calculated results suggested that the energy transfer pathway in C-PC monomer is predominant from ß-155 to ß-84 (1/K = 13.4 ps), however, from α-84 of one monomer to ß-84 (1/K = 0.3-0.4 ps) in a neighbor monomer in C-PC trimer. In C-PC hexamer, an additional energy flow was predicted to be from ß-155 (or α-84) in top trimer to adjacent ß-155 (or α-84) (1/K = 0.5-2.7 ps) in bottom trimer.


Asunto(s)
Simulación por Computador , Cianobacterias/química , Transferencia Resonante de Energía de Fluorescencia , Ficocianina/química , Estructura Molecular
15.
Bioorg Med Chem ; 21(11): 2826-31, 2013 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-23623712

RESUMEN

Cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphoshatase (Cy-FBP/SBPase) is an important target enzyme for finding inhibitors to solve harmful algal bloom (HAB). In this study, as potential inhibitors of Cy-FBP/SBPase, a series of novel chromone-connecting benzohydrazone compounds (Novel N'-((4-oxo-4H-chromen-3-yl)methylene)benzohydrazide) were designed and synthesized. Their inhibitory activities against Cy-FBP/SBPase were further examined in vitro. Some of these compounds, such as f6-f8, f11, f12 and f16, exhibit higher inhibitory activities (IC50=11.2-16.1 µM), especially, the compound f7 was identified as the most potent inhibitor with IC50 value of 11.2 µM. The probable binding-mode of compound f7 was further analyzed carefully by molecular docking methods. These results indicate that compound f7 could be used as a lead compound for further optimization and might have potential to be developed as a new algicide.


Asunto(s)
Antibacterianos/síntesis química , Proteínas Bacterianas/antagonistas & inhibidores , Cromonas/síntesis química , Cianobacterias/química , Fructosa-Bifosfatasa/antagonistas & inhibidores , Hidrazonas/síntesis química , Monoéster Fosfórico Hidrolasas/antagonistas & inhibidores , Antibacterianos/química , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Cromonas/química , Cianobacterias/enzimología , Diseño de Fármacos , Escherichia coli/genética , Fructosa-Bifosfatasa/química , Fructosa-Bifosfatasa/genética , Hidrazonas/química , Simulación del Acoplamiento Molecular , Monoéster Fosfórico Hidrolasas/química , Monoéster Fosfórico Hidrolasas/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética
16.
J Colloid Interface Sci ; 647: 344-353, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37267797

RESUMEN

The field of solar vapor generation has developed rapidly in recent years, but achieving the goals of a high evaporation rate, eco-friendliness and rapid preparation with low-cost raw materials is still a challenge. In this work, a type of photothermal hydrogel evaporator was prepared by blending eco-friendly poly(vinyl alcohol), agarose, Fe3+ and tannic acid (TA) together, in which the tannic acid-ferric ion (TA*Fe3+) complexes served as photothermal materials and effective gelators. The results indicate that the TA*Fe3+ complex exhibits excellent gelatinization ability and light-absorption performance, which leads to a compressive stress of 0.98 MPa at 80% strain and up to 85% light absorption ratio in the photothermal hydrogel. For interfacial evaporation, a high rate of 1.897 ± 0.11 kg·m-2·h-1 corresponding to an energy efficiency of 89.7 ± 2.73% under 1 sun irradiation is achieved. Moreover, the hydrogel evaporator exhibits high stability in a 12-hour test and a 20-cycle test without a decline in evaporation performance. The outdoor testing results show that the hydrogel evaporator can achieve an evaporation rate of > 0.70 kg/m2 and effectively purify wastewater treatment and seawater desalination.

17.
Pest Manag Sci ; 79(6): 2220-2229, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36750400

RESUMEN

BACKGROUND: To obtain new environmentally friendly fungicides, we used the natural product pimprinine as the lead compound, and designed and synthesized two series of ring-opening derivatives of pimprinine containing amide/thioamide. We then studied their antifungal activity against six common plant pathogenic fungi in vitro. RESULTS: Most of the target compounds have good antifungal activity against six important plant pathogenic fungi in vitro. At a concentration of 50 µg ml-1 , compound 3o showed prominent antifungal effects on Alternaria solani and Rhioctornia solani, with inhibition rates of 91.8% and 97.4%, and a 50% effective concentration (EC50 ) of 6.2255 and 0.6969 µg ml-1 respectively. The EC50 of compound 3o against Alternaria solani was significantly lower than that of boscalid (13.0380 µg ml-1 ) and flutriafol (11.9057 µg ml-1 ). In addition, compound 3o had good antifungal activity against Sclerotinia sclerotiorum, cucumber powdery mildew, cucumber Botrytis cinerea and Phytophthora capsici in vivo; the antifungal activity of compound 3o against cucumber Botrytis cinerea is 91.7%. At the same time, docking results for highly active compound 3o with the presumed target succinate dehydrogenase and the molecular docking prediction scores of all compounds further indicate its possible antifungal activity mechanism. CONCLUSION: The designed and optimized derivative 3o of ring-opening pimprinine has good antifungal activity and can be used as a new antifungal drug for further research. © 2023 Society of Chemical Industry.


Asunto(s)
Antifúngicos , Fungicidas Industriales , Oxazoles , Amidas/farmacología , Antifúngicos/química , Botrytis , Fungicidas Industriales/química , Simulación del Acoplamiento Molecular , Estructura Molecular , Relación Estructura-Actividad , Oxazoles/química
18.
J Chem Inf Model ; 52(7): 1833-41, 2012 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-22725250

RESUMEN

3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is a primary target in the current clinical treatment of hypercholesterolemia with specific inhibitors of "statin" family. Statins are excellent inhibitors of the class I (human) enzyme but relatively poor inhibitors of the class II enzyme, which are well-known as a potential target to discover drugs fighting against the invasive diseases originated from S. pneumoniae . However, no significantly effective inhibitors of class II HMGR have been reported so far. In the present study, the reasonable three-dimensional (3D) structure of class II HMGR from S. pneumoniae (SP-HMGR-II) was built by Swissmodel. On the basis of the modeling 3D structure in "close" flap domain form, several novel potential hit compounds out of SPECs database were picked out by using structure-based screening strategy. Especially the compounds 4, 3, and 11 exhibit highly inhibitory activities, with IC50 values of 11.5, 18.5, and 18.1 µM, respectively. Furthermore, the hit compounds were chosen as probe molecules, and their probable interactions with the corresponding individual residues have been examined by jointly using the molecular docking, site-directed mutagenesis, enzymatic assays, and fluorescence spectra, to provide an insight into a new special binding-model located between the HMG-CoA and NADPH pockets. The good agreement between theoretical and experimental results indicate that the modeling strategies and screening processes in the present study are very likely to be a promising way to search novel lead compounds with both structural diversity and high inhibitory activity against SP-HMGR-II in the future.


Asunto(s)
Diseño de Fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/química , Simulación de Dinámica Molecular , Streptococcus pneumoniae/efectos de los fármacos , Dominio Catalítico , Evaluación Preclínica de Medicamentos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Concentración 50 Inhibidora , Modelos Moleculares , Relación Estructura-Actividad
19.
J Phys Chem Lett ; 13(39): 9232-9237, 2022 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-36173107

RESUMEN

Hydrogen sulfide (H2S), as the third gasotransmitter, has an important impact on physiological and pathological activities. Herein, we fabricated an artificial nanochannel with a conductance value of 2.01 nS via a supramolecular coordination strategy. Benefiting from the unique H2S-mediated covalent reaction, the nanochannel biosensor could change from ON to OFF states with the addition of H2S. Furthermore, this nanochannel directed the ion transport, showing a high rectification ratio as well as gating ratio. Subsequently, theoretical simulations were conducted to help to reveal the possible mechanism of the functionalized nanochannel. This study can provide insights for better understanding the process of H2S-regulated biological channels and fabricating gas gated nanofluids.


Asunto(s)
Técnicas Biosensibles , Gasotransmisores , Sulfuro de Hidrógeno , Transporte Iónico
20.
ACS Appl Mater Interfaces ; 14(39): 44809-44820, 2022 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-36162058

RESUMEN

Cost management and scalable fabrication without sacrificing the purification performance are two critical issues that should be addressed before the practical commercial application of solar-driven evaporators. To address this challenge, we report a porous photothermal hydrogel coating prepared by mixing the raw materials of sawdust (SD), carbon nanotubes (CNTs), and poly(vinyl alcohol) (PVA), which was applied to undergo a blading-drying-rehydration process to prepare the evaporator. In the coating, the crystallized PVA gives the coating a solid skeleton and the sawdust endows the coating with a loose structure to sufficiently enhance the water transportation capacity. As a result, the evaporator coated with the hydrogel coating displays a high water transport rate and efficient evaporation performance along with excellent mechanical properties and stability. Water migrates vertically upward 5 cm within 4 minutes. The compressive stress of the rehydrated hydrogel coating reaches as high as 14.28 MPa under 80% strain. The water evaporation rate of the hydrogel coating-based evaporator reaches 1.833 kg m-2 h-1 corresponding to an energy efficiency of 83.29% under 1 sun irradiation. What is more, the hydrogel coating retains its excellent evaporation performance and stability after immersion in acid or alkali solution, ultrasound treatment, and long-time immersion in water. Under outdoor conditions, the water evaporation rate of the hydrogel coating-based evaporator is about 5.69 times higher than that of pure water. This study proposes a rapid, cost-effective, and scalable strategy for preparing a high-performance photothermal hydrogel coating that will find sustainable and practical application in solar-driven water purification.

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