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1.
Mol Divers ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727994

RESUMO

Herein, a novel series of naphthamide derivatives has been rationally developed, synthesized, and evaluated for their inhibitory activity against monoamine oxidase (MAO) and cholinesterase (ChE) enzymes. Compared to the reported naphthalene-based hit IV, the new naphthamide hybrids 2a, 2c, 2g and 2h exhibited promising MAO inhibitory activities; with an IC50 value of 0.294 µM, compound 2c most potently inhibited MAO-A, while compound 2g exhibited most potent MAO-B inhibitory activity with an IC50 value of 0.519 µM. Compounds 2c and 2g showed selectivity index (SI) values of 6.02 for MAO-A and 2.94 for MAO-B, respectively. On the other hand, most compounds showed weak inhibitory activity against ChEs except 2a and 2h over butyrylcholinesterase (BChE). The most potent compounds 2c and 2g were found to be competitive and reversible MAO inhibitors based on kinetic and reversibility studies. Plausible interpretations of the observed biological effects were provided through molecular docking simulations. The drug-likeness predicted by SwissADME and Osiris property explorer showed that the most potent compounds (2a, 2c, 2g, and 2h) obey Lipinski's rule of five. Accordingly, in the context of neurological disorders, hybrids 2c and 2g may contribute to the identification of safe and potent therapeutic approaches in the near future.

2.
Molecules ; 28(16)2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37630420

RESUMO

Monoamine oxidase (MAO, EC 1.4.3.4) is responsible for the oxidative breakdown of both endogenous and exogenous amines and exists in MAO-A and MAO-B isomers. Eighteen indole-based phenylallylidene derivatives were synthesized via nucleophilic addition reactions comprising three sub-series, IHC, IHMC, and IHNC, and were developed and examined for their ability to inhibit MAO. Among them, compound IHC3 showed a strong MAO-B inhibitory effect with an IC50 (half-maximal inhibitory concentration) value of 1.672 µM, followed by IHC2 (IC50 = 16.934 µM). Additionally, IHC3 showed the highest selectivity index (SI) value of >23.92. The effectiveness of IHC3 was lower than the reference pargyline (0.14 µM); however, the SI value was higher than pargyline (17.16). Structurally, the IHC (-H in the B-ring) sub-series exhibited relatively stronger MAO-B inhibition than the others. In the IHC series, IHC3 (-F in the A-ring) exhibited stronger MAO-B suppression than the other substituted derivatives in the order -F > -Br > -Cl > -OCH3, -CH3, and -H at the 2-position in the A-ring. In the reversibility and enzyme kinetics experiments, IHC3 was a reversible inhibitor with a Ki value of 0.51 ± 0.15 µM for MAO-B. Further, it was observed that IHC3 greatly decreased the cell death caused by rotenone in SH-SY5Y neuroblastoma cells. A molecular docking study of the lead molecule was also performed to determine hypothetical interactions in the enzyme-binding cavity. These findings suggest that IHC3 is a strong, specific, and reversible MAO-B inhibitor that can be used to treat neurological diseases.


Assuntos
Antipsicóticos , Isatina , Neuroblastoma , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Micro-Ondas , Simulação de Acoplamento Molecular , Pargilina , Farmacóforo , Dopaminérgicos , Monoaminoxidase
3.
Sensors (Basel) ; 22(14)2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35890859

RESUMO

A highly polarizable moisture sensor with multimodal sensing capabilities has great advantages for healthcare applications such as human respiration monitoring. We introduce an ionically polarizable moisture sensor based on NaCl/BaTiO3 composite films fabricated using a facile aerosol deposition (AD) process. The proposed sensing model operates based on an enormous NaCl ionization effect in addition to natural moisture polarization, whereas all previous sensors are based only on the latter. We obtained an optimal sensing performance in a 0.5 µm-thick layer containing NaCl-37.5 wt% by manipulating the sensing layer thickness and weight fraction of NaCl. The NaCl/BaTiO3 sensing layer exhibits outstanding sensitivity over a wide humidity range and a fast response/recovery time of 2/2 s; these results were obtained by performing the one-step AD process at room temperature without using any auxiliary methods. Further, we present a human respiration monitoring system using a sensing device that provides favorable and stable electrical signals under diverse respiratory scenarios.


Assuntos
Taxa Respiratória , Cloreto de Sódio , Aerossóis , Humanos , Umidade , Monitorização Fisiológica
4.
J Environ Manage ; 301: 113860, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34626947

RESUMO

Humans face threats from air pollutants present in both indoor and outdoor environments. The emerging role of plants in remediating the atmospheric environment is now being actively investigated as a possible solution for this problem. Foliar surfaces of plants (e.g., the leaves of cotton) can absorb a variety of airborne pollutants (e.g., formaldehyde, benzene, trimethylamine, and xylene), thereby reducing their concentrations in indoor environments. Recently, theoretical and experimental studies have been conducted to offer better insights into the interactions between plants and the surrounding air. In our research, an overview on the role of plants in reducing air pollution (often referred to as phytoremediation) is provided based on a comprehensive literature survey. The major issues for plant-based research for the reduction of air pollution in both outdoor and indoor environments are discussed in depth along with future challenges. Analysis of the existing data confirms the effectiveness of phytoremediation in terms of the absorption and purification of pollutants (e.g., by the leaves and roots of plants and trees), while being controlled by different variables (e.g., pore characteristics and planting patterns). Although most lab-scale studies have shown that plants can effectively absorb pollutants, it is important for such studies to reflect the real-world conditions, especially with the influence of human activities. Under such conditions, pollutants are to be replenished continually while the plant surface area to ambient atmosphere volume ratio vastly decreases (e.g., relative to lab-based experiments). The replication of such experimental conditions is the key challenge in this field of research. This review is expected to offer valuable insights into the innate ability of various plants in removing diverse pollutants (such as formaldehyde, benzene, and particulate matter) under different environmental settings.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluição do Ar/prevenção & controle , Poluição do Ar em Ambientes Fechados/análise , Humanos , Material Particulado/análise , Plantas
5.
Molecules ; 27(12)2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35744926

RESUMO

Sixteen compounds (TR1-TR16) were synthesized and evaluated for their inhibitory activities against monoamine oxidase A and B (MAOs). Most of the derivatives showed potent and highly selective MAO-B inhibition. Compound TR16 was the most potent inhibitor against MAO-B with an IC50 value of 0.17 µM, followed by TR2 (IC50 = 0.27 µM). TR2 and TR16 selectivity index (SI) values for MAO-B versus MAO-A were 84.96 and higher than 235.29, respectively. Compared to the basic structures, the para-chloro substituent in TR2 and TR16 increased the inhibitory activity of MAO-B. TR2 and TR16 were reversible MAO-B inhibitors that were competitive, with Ki values of 0.230 ± 0.004 and 0.149 ± 0.016 µM, respectively. The PAMPA method indicated that compounds TR2 and TR16 had the tendency to traverse the blood-brain barrier. Docking investigations revealed that lead compounds were beneficial for MAO-B inhibition via association with key as well as selective E84 or Y326 residues, but not for MAO-A inhibition via interaction primarily driven by hydrophobic contacts. In conclusion, TR2 and TR16 are therapeutic prospects for the management of multiple neurodegenerative diseases.


Assuntos
Inibidores da Monoaminoxidase , Monoaminoxidase , Dopaminérgicos/farmacologia , Cinética , Simulação de Acoplamento Molecular , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/farmacologia , Relação Estrutura-Atividade
6.
Molecules ; 28(1)2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36615451

RESUMO

Thirteen compounds were isolated from the Canavalia lineata pods and their inhibitory activities against human monoamine oxidase-A (hMAO-A) and -B (hMAO-B) were evaluated. Among them, compounds 8 (medicarpin) and 13 (homopterocarpin) showed potent inhibitory activity against hMAO-B (IC50 = 0.45 and 0.72 µM, respectively) with selectivity index (SI) values of 44.2 and 2.07, respectively. Most of the compounds weakly inhibited MAO-A, except 9 (prunetin) and 13. Compounds 8 and 13 were reversible competitive inhibitors against hMAO-B (Ki = 0.27 and 0.21 µM, respectively). Structurally, the 3-OH group at A-ring of 8 showed higher hMAO-B inhibitory activity than 3-OCH3 group at the A-ring of 13. However, the 9-OCH3 group at B-ring of 13 showed higher hMAO-B inhibitory activity than 8,9-methylenedioxygroup at the B-ring of 12 (pterocarpin). In cytotoxicity study, 8 and 13 showed non-toxicity to the normal (MDCK) and cancer (HL-60) cells and moderate toxicity to neuroblastoma (SH-SY5Y) cell. Molecular docking simulation revealed that the binding affinities of 8 and 13 for hMAO-B (-8.7 and -7.7 kcal/mol, respectively) were higher than those for hMAO-A (-3.4 and -7.1 kcal/mol, respectively). These findings suggest that compounds 8 and 13 be considered potent reversible hMAO-B inhibitors to be used for the treatment of neurological disorders.


Assuntos
Inibidores da Monoaminoxidase , Neuroblastoma , Humanos , Inibidores da Monoaminoxidase/química , Canavalia , Simulação de Acoplamento Molecular , Monoaminoxidase/metabolismo , Relação Estrutura-Atividade
7.
Int Arch Occup Environ Health ; 94(7): 1605-1615, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34089350

RESUMO

PURPOSE: We aimed to investigate the association between air pollution concentration levels and hospital admissions for heart failure (HF) among older adults in metropolitan cities in South Korea. METHODS: We used hospital admission data of 1.8 million older adults in seven metropolitan cities from 2008 to 2016, derived from the National Health Insurance Service of South Korea. Daily HF admission data were linked to air pollutants concentrations for the respective dates, including particulate matter less than 2.5 µm in size (PM2.5), 10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone. We estimated the association between air pollutants and daily HF admissions using quasi-Poisson generalized additive models for each city. RESULTS: During the study period, 142,490 hospital admissions for HF were noted. Increases of 10 µg/m3 of PM2.5 and PM10, and 10 ppb of SO2, NO2, and CO were associated with an increased risk of HF admission by 0.93% ([95% confidence intervals 0.51-1.36], 0.55% [0.31-0.80], 6.04% [2.15-10.08], 1.10% [0.38-1.82], and 0.05% [0.01-0.09]), respectively, on the same day. Increases in mean exposure to PM2.5, PM10, and SO2 for 8 days from the concurrent day were also significantly associated with HF admissions. During the warm season, the risk of HF admissions increased shortly after an increase in PM2.5, whereas prolonged effects were observed during the cold season. CONCLUSION: Our study suggests the adverse effects of air pollution on HF. Moreover, the evidence of seasonality may help tailor protection guidelines for older adults.


Assuntos
Poluição do Ar/análise , Exposição Ambiental , Insuficiência Cardíaca/epidemiologia , Hospitalização/estatística & dados numéricos , Poluentes Atmosféricos/análise , Monóxido de Carbono/análise , Cidades/epidemiologia , Humanos , Dióxido de Nitrogênio/análise , Ozônio/análise , Material Particulado/análise , República da Coreia/epidemiologia , Estações do Ano , Dióxido de Enxofre/análise
8.
Int J Mol Sci ; 22(23)2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34884628

RESUMO

Four chitinases were cloned and characterized from three strains isolated from a mudflat: Aeromonas sp. SK10, Aeromonas sp. SK15, and Chitinibacter sp. SK16. In SK10, three genes, Chi18A, Pro2K, and Chi19B, were found as a cluster. Chi18A and Chi19B were chitinases, and Pro2K was a metalloprotease. With combinatorial amplification of the genes and analysis of the hydrolysis patterns of substrates, Chi18A and Chi19B were found to be an endochitinase and exochitinase, respectively. Chi18A and Chi19B belonged to the glycosyl hydrolase family 18 (GH18) and GH19, with 869 and 659 amino acids, respectively. Chi18C from SK15 belonged to GH18 with 864 amino acids, and Chi18D from SK16 belonged to GH18 with 664 amino acids. These four chitinases had signal peptides and high molecular masses with one or two chitin-binding domains and, interestingly, preferred alkaline conditions. In the activity staining, their sizes were determined to be 96, 74, 95, and 73 kDa, respectively, corresponding to their expected sizes. Purified Chi18C and Chi18D after pET expression produced N,N'-diacetylchitobiose as the main product in hydrolyzing chitooligosaccharides and colloidal chitin. These results suggest that Chi18A, Chi18C, and Chi18D are endochitinases, that Chi19B is an exochitinase, and that these chitinases can be effectively used for hydrolyzing natural chitinous sources.


Assuntos
Aeromonas/enzimologia , Proteínas de Bactérias/metabolismo , Betaproteobacteria/enzimologia , Quitina/metabolismo , Quitinases/metabolismo , Sedimentos Geológicos/química , Aeromonas/isolamento & purificação , Betaproteobacteria/isolamento & purificação , Hidrólise , Filogenia
9.
Molecules ; 26(19)2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34641548

RESUMO

A small series of nitro group-bearing enamides was designed, synthesized (NEA1-NEA5), and evaluated for their inhibitory profiles of monoamine oxidases (MAOs) and ß-site amyloid precursor protein cleaving enzyme 1 (ß-secretase, BACE1). Compounds NEA3 and NEA1 exhibited a more potent MAO-B inhibition (IC50 value = 0.0092 and 0.016 µM, respectively) than the standards (IC50 value = 0.11 and 0.14 µM, respectively, for lazabemide and pargyline). Moreover, NEA3 and NEA1 showed greater selectivity index (SI) values toward MAO-B over MAO-A (SI of >1652.2 and >2500.0, respectively). The inhibition and kinetics studies suggested that NEA3 and NEA1 are reversible and competitive inhibitors with Ki values of 0.013 ± 0.005 and 0.0049 ± 0.0002 µM, respectively, for MAO-B. In addition, both NEA3 and NEA1 showed efficient BACE1 inhibitions with IC50 values of 8.02 ± 0.13 and 8.21 ± 0.03 µM better than the standard quercetin value (13.40 ± 0.04 µM). The parallel artificial membrane permeability assay (PAMPA) method demonstrated that all the synthesized derivatives can cross the blood-brain barrier (BBB) successfully. Docking analyses were performed by employing an induced-fit docking approach in the GLIDE module of Schrodinger, and the results were in agreement with their in vitro inhibitory activities. The present study resulted in the discovery of potent dual inhibitors toward MAO-B and BACE1, and these lead compounds can be fruitfully explored for the generation of newer, clinically active agents for the treatment of neurodegenerative disorders.


Assuntos
Amidas/química , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Inibidores da Monoaminoxidase/química , Monoaminoxidase/química , Inibidores de Proteases/química , Amidas/síntese química , Amidas/metabolismo , Barreira Hematoencefálica/metabolismo , Membranas Artificiais , Estrutura Molecular , Inibidores da Monoaminoxidase/metabolismo , Inibidores de Proteases/metabolismo
10.
Molecules ; 26(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071665

RESUMO

Halogens have been reported to play a major role in the inhibition of monoamine oxidase (MAO), relating to diverse cognitive functions of the central nervous system. Pyrazoline/halogenated pyrazolines were investigated for their inhibitory activities against human monoamine oxidase-A and -B. Halogen substitutions on the phenyl ring located at the fifth position of pyrazoline showed potent MAO-B inhibition. Compound 3-(4-ethoxyphenyl)-5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole (EH7) showed the highest potency against MAO-B with an IC50 value of 0.063 µM. The potencies against MAO-B were increased in the order of -F (in EH7) > -Cl (EH6) > -Br (EH8) > -H (EH1). The residual activities of most compounds for MAO-A were > 50% at 10 µM, except for EH7 and EH8 (IC50 = 8.38 and 4.31 µM, respectively). EH7 showed the highest selectivity index (SI) value of 133.0 for MAO-B, followed by EH6 at > 55.8. EH7 was a reversible and competitive inhibitor of MAO-B in kinetic and reversibility experiments with a Ki value of 0.034 ± 0.0067 µM. The molecular dynamics study documented that EH7 had a good binding affinity and motional movement within the active site with high stability. It was observed by MM-PBSA that the chirality had little effect on the overall binding of EH7 to MAO-B. Thus, EH7 can be employed for the development of lead molecules for the treatment of various neurodegenerative disorders.


Assuntos
Simulação de Dinâmica Molecular , Inibidores da Monoaminoxidase/química , Pirazóis/química , Barreira Hematoencefálica/efeitos dos fármacos , Domínio Catalítico , Química Farmacêutica/métodos , Cognição/efeitos dos fármacos , Desenho de Fármacos , Halogênios/química , Humanos , Concentração Inibidora 50 , Cinética , Modelos Químicos , Simulação de Acoplamento Molecular , Estrutura Molecular , Monoaminoxidase/metabolismo , Movimento (Física) , Análise de Componente Principal , Ligação Proteica , Proteínas Recombinantes/química , Estereoisomerismo , Relação Estrutura-Atividade
11.
Neurochem Res ; 45(8): 1930-1940, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32440903

RESUMO

The antidepressant activities of hispidol and decursin (both potent monoamine oxidase A (MAO-A) inhibitors) were evaluated using the forced swimming test (FST) and the tail suspension test (TST) in mice, and thereafter, levels of neurotransmitter monoamines and metabolites in brain tissues were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Hispidol (15 mg/kg) caused less or comparable immobility than fluoxetine (15 mg/kg; the positive control) in immobility time, as determined by FST (9.6 vs 32.0 s) and TST (53.1 vs 48.7 s), respectively, and its effects were dose-dependent and significant. Decursin (15 mg/kg) also produced immobility comparable to that of fluoxetine as determined by FST (47.0 vs 43.4 s) and TST (55.6 vs 63.4 s), and its effects were also dose-dependent and significant. LC-MS/MS analysis after FST showed that hispidol (15 mg/kg) greatly increased dopamine (DA) and serotonin levels dose-dependently in brain tissues as compared with the positive control. Decursin (15 mg/kg) dose-dependently increased DA level after TST. Slight changes in norepinephrine and 3,4-dihydroxyphenylacetic acid levels were observed after FST and TST in hispidol- or decursin-treated animals. It was observed that hispidol and decursin were effective and comparable to fluoxetine in immobility tests. These immobility and monoamine level results suggest that hispidol and decursin are potential antidepressant agents for the treatment of depression, and that they act mainly through serotonergic and/or dopaminergic systems.


Assuntos
Antidepressivos/uso terapêutico , Benzofuranos/uso terapêutico , Benzopiranos/uso terapêutico , Compostos de Benzilideno/uso terapêutico , Butiratos/uso terapêutico , Depressão/tratamento farmacológico , Dopamina/metabolismo , Serotonina/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Elevação dos Membros Posteriores , Masculino , Camundongos Endogâmicos ICR , Inibidores da Monoaminoxidase/uso terapêutico , Natação
12.
Molecules ; 25(22)2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33212876

RESUMO

Twelve pyridazinones (T1-T12) containing the (2-fluorophenyl) piperazine moiety were designed, synthesized, and evaluated for monoamine oxidase (MAO) -A and -B inhibitory activities. T6 was found to be the most potent MAO-B inhibitor with an IC50 value of 0.013 µM, followed by T3 (IC50 = 0.039 µM). Inhibitory potency for MAO-B was more enhanced by meta bromo substitution (T6) than by para bromo substitution (T7). For para substitution, inhibitory potencies for MAO-B were as follows: -Cl (T3) > -N(CH3)2 (T12) > -OCH3 (T9) > Br (T7) > F (T5) > -CH3 (T11) > -H (T1). T6 and T3 efficiently inhibited MAO-A with IC50 values of 1.57 and 4.19 µM and had the highest selectivity indices (SIs) for MAO-B (120.8 and 107.4, respectively). T3 and T6 were found to be reversible and competitive inhibitors of MAO-B with Ki values of 0.014 and 0.0071, respectively. Moreover, T6 was less toxic to healthy fibroblast cells (L929) than T3. Molecular docking simulations with MAO binding sites returned higher docking scores for T6 and T3 with MAO-B than with MAO-A. These results suggest that T3 and T6 are selective, reversible, and competitive inhibitors of MAO-B and should be considered lead candidates for the treatment of neurodegenerative disorders like Alzheimer's disease.


Assuntos
Desenho de Fármacos , Inibidores da Monoaminoxidase/síntese química , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/metabolismo , Piperazina/síntese química , Piperazina/farmacologia , Piridazinas/síntese química , Piridazinas/farmacologia , Animais , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Morte Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cinética , Camundongos , Simulação de Acoplamento Molecular , Inibidores da Monoaminoxidase/química , Piperazina/química , Espectroscopia de Prótons por Ressonância Magnética , Piridazinas/química , Proteínas Recombinantes/metabolismo
13.
Molecules ; 25(10)2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32443652

RESUMO

Previously synthesized novel chalcone oxime ethers (COEs) were evaluated for inhibitory activities against monoamine oxidases (MAOs) and acetylcholinesterase (AChE). Twenty-two of the 24 COEs synthesized, except COE-17 and COE-24, had potent and/or significant selective inhibitory effects on MAO-B. COE-6 potently inhibited MAO-B with an IC50 value of 0.018 µM, which was 105, 2.3, and 1.1 times more potent than clorgyline, lazabemide, and pargyline (reference drugs), respectively. COE-7, and COE-22 were also active against MAO-B, both had an IC50 value of 0.028 µM, which was 67 and 1.5 times lower than those of clorgyline and lazabemide, respectively. Most of the COEs exhibited weak inhibitory effects on MAO-A and AChE. COE-13 most potently inhibited MAO-A (IC50 = 0.88 µM) and also significantly inhibited MAO-B (IC50 = 0.13 µM), and it could be considered as a potential nonselective MAO inhibitor. COE-19 and COE-22 inhibited AChE with IC50 values of 5.35 and 4.39 µM, respectively. The selectivity index (SI) of COE-22 for MAO-B was higher than that of COE-6 (SI = 778.6 vs. 222.2), but the IC50 value (0.028 µM) was slightly lower than that of COE-6 (0.018 µM). In reversibility experiments, inhibitions of MAO-B by COE-6 and COE-22 were recovered to the levels of reference reversible inhibitors and both competitively inhibited MAO-B, with Ki values of 0.0075 and 0.010 µM, respectively. Our results show that COE-6 and COE-22 are potent, selective MAO-B inhibitors, and COE-22 is a candidate of dual-targeting molecule for MAO-B and AChE.


Assuntos
Chalcona/química , Inibidores da Colinesterase/química , Inibidores da Monoaminoxidase/química , Oximas/química , Acetilcolinesterase/química , Acetilcolinesterase/efeitos dos fármacos , Chalcona/farmacologia , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Éteres/química , Éteres/farmacologia , Humanos , Cinética , Monoaminoxidase/química , Monoaminoxidase/efeitos dos fármacos , Inibidores da Monoaminoxidase/isolamento & purificação , Inibidores da Monoaminoxidase/farmacologia , Oximas/farmacologia
14.
Nanotechnology ; 30(3): 035203, 2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30422810

RESUMO

In this research, we propose a nanoscale and embeddable subzero temperature sensor that is made with a temperature-dependent titanium-oxide based metal-insulator-transition (MIT) device. For a nanoscale two-terminal structured MIT device, the MIT device's characteristics are noticeably changed from abrupt to gradual MIT under zero temperature, which is called MIT deformation. On the basis of the MIT deformation characteristics, subzero temperatures can be detected by reading current levels as temperature changes. Furthermore, this sensor has desirable sensing properties such as high-linearity and proper sensitivity. The obtained results strongly show that titanium-oxides with CMOS process compatibility, cost-effectiveness, nontoxicity, etc, can be applied at the nanoscale and embeddable on subzero temperature sensors on a chip.

15.
Bioorg Chem ; 93: 103335, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31606547

RESUMO

The present study documents the synthesis of oxygenated chalcone (O1-O26) derivatives and their abilities to inhibit monoamine oxidases. All 26 derivatives examined showed potent inhibitory activity against MAO-B. Compound O23 showed the greatest inhibitory activity against MAO-B with an IC50 value of 0.0021 µM, followed by compounds O10 and O17 (IC50 = 0.0030 and 0.0034 µM, respectively). In addition, most of the derivatives potently inhibited MAO-A and O6 was the most potent inhibitor with an IC50 value of 0.029 µM, followed by O3, O4, O9, and O2 (IC50 = 0.035, 0.053, 0.072, and 0.082 µM, respectively). O23 had a high selectivity index (SI) value for MAO-B of 138.1, and O20 (IC50 value for MAO-B = 0.010 µM) had an extremely high SI of >4000. In dialysis experiments, inhibitions of MAO-A and MAO-B by O6 and O23, respectively, were recovered to their respective reversible reference levels, demonstrating both are reversible inhibitors. Kinetic studies revealed that O6 and O23 competitively inhibited MAO-A and MAO-B, respectively, with respective Ki values of 0.016 ±â€¯0.0007 and 0.00050 ±â€¯0.00003 µM. Lead compound are also non-toxic at 200 µg/mL in normal rat spleen cells. Molecular docking simulations and subsequent Molecular Mechanics/Generalized Born Surface Area calculations provided a rationale that explained experimental data.


Assuntos
Chalconas/química , Desenho de Fármacos , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/efeitos dos fármacos , Oxigênio/química , Animais , Cinética , Simulação de Acoplamento Molecular , Inibidores da Monoaminoxidase/síntese química , Ratos , Baço/citologia , Baço/efeitos dos fármacos , Relação Estrutura-Atividade
16.
Bioorg Chem ; 89: 103043, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31200287

RESUMO

Six hundred forty natural compounds were tested for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Of those, sargachromanol I (SCI) and G (SCG) isolated from the brown alga Sargassum siliquastrum, dihydroberberine (DB) isolated from Coptis chinensis, and macelignan (ML) isolated from Myristica fragrans, potently and effectively inhibited AChE with IC50 values of 0.79, 1.81, 1.18, and 4.16 µM, respectively. SCI, DB, and ML reversibly inhibited AChE and showed mixed, competitive, and noncompetitive inhibition, respectively, with Ki values of 0.63, 0.77, and 4.46 µM, respectively. Broussonin A most potently inhibited BChE (IC50 = 4.16 µM), followed by ML, SCG, and SCI (9.69, 10.79, and 13.69 µM, respectively). In dual-targeting experiments, ML effectively inhibited monoamine oxidase B with the greatest potency (IC50 = 7.42 µM). Molecular docking simulation suggested the binding affinity of SCI (-8.6 kcal/mol) with AChE was greater than those of SCG (-7.9 kcal/mol) and DB (-8.2 kcal/mol). Docking simulation indicated SCI interacts with AChE at Trp81, and that SCG interacts at Ser119. No hydrogen bond was predicted for the interaction between AChE and DB. This study suggests SCI, SCG, DB, and ML be viewed as new reversible AChE inhibitors and useful lead compounds for the development for the treatment of Alzheimer's disease.


Assuntos
Acetilcolinesterase/metabolismo , Benzopiranos/farmacologia , Produtos Biológicos/farmacologia , Inibidores da Colinesterase/farmacologia , Álcoois Graxos/farmacologia , Sargassum/química , Anemarrhena/química , Animais , Benzopiranos/química , Benzopiranos/isolamento & purificação , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Relação Dose-Resposta a Droga , Electrophorus , Álcoois Graxos/química , Álcoois Graxos/isolamento & purificação , Cavalos , Humanos , Cinética , Simulação de Acoplamento Molecular , Estrutura Molecular , Monoaminoxidase/metabolismo , Myristica/química , Relação Estrutura-Atividade
17.
J Nanosci Nanotechnol ; 19(7): 4330-4332, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30765015

RESUMO

Sensors and electronic devices based on semiconductors in their two-dimensional forms have many advantages. In this paper, we studied micro-Hall sensors based on two-dimensional molybdenum diselenide for the first time. The micro-Hall sensor based on a Ti/MoSe2/Ti structure clearly showed a linear dependence of the Hall voltage as a function of the magnetic field, with a magnetic sensitivity of ∼16 V/AT. The magnetic sensitivity was higher in the Au/MoSe2/Au structure, with a maximum value of ∼120 V/AT at a bias current of 100 mA; the minimum detectable magnetic field was found to be 1.45 µT/Hz1/2 at the same current value, making our new micro-Hall sensor a very good candidate for magnetic sensing applications.

18.
J Nanosci Nanotechnol ; 19(2): 1151-1154, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30360222

RESUMO

A new immobilization technique of nanoscale TiO2 powders to expanded polystryrene (EPS) balls with temperature-controlled melting method was validated for mass production, and the photocatalytic activity of TiO2 powder-embedded EPS (TiEPS) balls using methylene blue (MB) solution with different concentrations under ultraviolet irradiation and under the natural solar light irradiation. Whereas MB molecules were weakly adsorbed onto the surface of both TiO2 powders and supporting polymers without any specific interactions, the photocatalytic efficiency of TiEPS balls with UV (Kapp =0.016~0.043 min-1) was greater through coupled reaction processes (adsorption, photolysis, and photocatalysis). After 5-min sonication, more TiO2 powders on the TiEPS balls can be involved into the both adsorption and photocatalytic reactions of MB, and can increase the MB removal efficiencies. TiEPS balls can be reused for several consecutive runs without any significant decrease in photocatalytic activity until the recalcitrant contaminants were completely coated on the surface of TiEPS balls and loss of TiO2 powders embedded on the surface of TiEPS balls was significant. Based on the aforementioned results, self-floating TiEPS balls manufactured from this simple and cost-effective melting method can be used to remove the organic contaminants and to inhibit the excessive growth of harmful algae in the stagnant water body.

19.
Arch Environ Contam Toxicol ; 74(2): 298-304, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28975388

RESUMO

Eight metals were analyzed in the pellet of Eurasian eagle owls (Bubo bubo) breeding in Korea: Paju, Ganghwa, Gimpo, and Sihwa, Gyeonggi-do (N = 15, respectively). Except for cadmium (Cd), concentrations of all metals differed among sites (ANOVA, p < 0.001); Sihwa had relatively higher metal concentrations compared with other sites. Clutch size did not differ among the four sites. However, Sihwa had the greatest nesting success and number of fledglings (per hatchlings and laid egg) and highest mean weight of diet. Lead concentrations in the pellets were generally lower than the excrements of various birds worldwide. We suggest that all metal concentrations in pellets do not negatively affect the reproduction of Eurasian eagle owls, and food supply at Sihwa seems likely more important to breeding success than metal contamination.


Assuntos
Poluentes Ambientais/análise , Fezes/química , Metais/análise , Estrigiformes/fisiologia , Animais , Tamanho da Ninhada , Exposição Ambiental/análise , Chumbo/análise , Reprodução , República da Coreia
20.
Molecules ; 23(12)2018 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-30477128

RESUMO

One hundred and seventy seven acetone extracts of lichen and 258 ethyl acetate extracts of cultured lichen-forming fungi (LFF) were screened for antimicrobial activity against Staphylococcus aureus and Enterococcus faecium using a disk diffusion method. Divaricatic acid was isolated from Evernia mesomorpha and identified by LC-MS, ¹H-, 13C- and DEPT-NMR. Purified divaricatic acid was effective against Gram + bacteria, such as Bacillus subtilis, Staphylococcus epidermidis, Streptococcus mutans, and Enterococcus faecium, with the minimum inhibitory concentration (MIC) values ranging from 7.0 to 64.0 µg/mL, whereas vancomycin was effective in the MICs ranging from 0.78 to 25.0 µg/mL. Interestingly, the antibacterial activity of divaricatic acid was higher than vancomycin against S. epidermidis and E. faecium, and divaricatic acid was active against Candida albicans. In addition, divaricatic acid was active as vancomycin against S. aureus (3A048; an MRSA). These results suggested that divaricatic acid is a potential antimicrobial agent for the treatment of MRSA infections.


Assuntos
Anti-Infecciosos/farmacologia , Depsídeos/farmacologia , Líquens/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Extratos Vegetais/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Depsídeos/química , Depsídeos/isolamento & purificação , Testes de Sensibilidade Microbiana , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação
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