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1.
Talanta ; 236: 122884, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635264

RESUMO

This work describes (Z)-N-((Z)-2-(1,3,3-trimethylindolin-2ylidene)ethylidene)quinoline-8-amine (LYSO-QF), a high-performing and biocompatible dye comprised of quinoline and Fisher aldehyde moieties linked via an imine vinyl backbone with lysosome targeting ability that can be used to quantitatively detect the mercury ion (Hg2+) in biosystems and the natural environment. This is achieved by forming three different tetrameric, trimeric and dimeric complexes between Hg2+ and LYSO-QF with the limit of detection (LOD) of 11 nm. The complexes formed were analyzed with the aid of time-dependent density functional theory (TD-DFT) calculations. The concentration dependence of the Hg2+ complex fluorescence emission changes from grey-green to jade green and then to red as the different types of complex are formed. The favorable sensor properties of the LYSO-QF probe are demonstrated by monitoring different Hg2+ concentrations in buffer solutions, HeLa cells, zebrafish model samples and several different types of water sample. Experiments with Whatman paper strips demonstrate that the cost-effective LYSO-QF also has considerable potential for use in on-site Hg2+ detection with the naked eye.


Assuntos
Complexos de Coordenação , Mercúrio , Quinolinas , Aldeídos , Animais , Células HeLa , Humanos , Lisossomos , Peixe-Zebra
2.
Appl Microbiol Biotechnol ; 105(18): 6871-6886, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34477940

RESUMO

Aspergillus flavus is a notorious saprophytic fungus that compromises the quantity and quality of postharvest grains and produces carcinogenic aflatoxins. The natural compound hexanal disrupts cell membrane synthesis and mitochondrial function and induces apoptosis in A. flavus; here, we investigated the molecular mechanisms underlying these effects. The minimum inhibition and fungicidal concentration (MIC and MFC) of hexanal against A. flavus spores were 3.2 and 9.6 µL/mL, respectively. Hexanal exposure resulted in abnormal spore morphology and early spore apoptosis. These changes were accompanied by increased reactive oxygen species production, reduced mitochondrial membrane potential, and DNA fragmentation. Transcriptomic analysis revealed that hexanal treatment greatly altered the metabolism of A. flavus spores, including membrane permeability, mitochondrial function, energy metabolism, DNA replication, oxidative stress, and autophagy. This study provides novel insights into the mechanism underlying the antifungal activity of hexanal, suggesting that hexanal can be used an anti-A. flavus agent for agricultural applications. KEY POINTS: • Hexanal exposure resulted in abnormal spore morphology. • The apoptotic characteristics of A. flavus were induced after hexanal treatment. • Hexanal could change the expression of key A. flavus growth-related genes.


Assuntos
Aflatoxinas , Aspergillus flavus , Aflatoxinas/metabolismo , Aldeídos , Antifúngicos/metabolismo , Antifúngicos/farmacologia , Apoptose , Mitocôndrias , Esporos Fúngicos/metabolismo
3.
Enzyme Microb Technol ; 150: 109866, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34489025

RESUMO

A novel Geotrichum candidum aldehyde dehydrogenase (GcALDH) effectively oxidized aldehydes to carboxylic acids under mild conditions. Nonetheless, the free form of GcALDH still had a limitation in stability and recyclability. Herein, to overcome these limitations, this study achieved the immobilization of the GcALDH by the organic-inorganic nanocrystal formation. The GcALDH nanocrystal exhibited 261 ± 40 % of activity comparing to the free enzyme. It also exhibited improved thermostability and recyclability as well as remained excellent substrate promiscuity, which suggested its potential use in green industries. To the best of our knowledge, this is the first time to report the ALDH-inorganic nanocrystal formation with superior properties.


Assuntos
Geotrichum , Nanopartículas , Aldeído Desidrogenase , Aldeídos
4.
Talanta ; 235: 122722, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34517590

RESUMO

In-vehicle air pollution has become a major concern to public health in recent years. The traditional analytical methods for detection of volatile organic compounds (VOCs) pollutants in air are based on gas chromatography - mass spectrometry (GC-MS) or high-performance liquid chromatography (HPLC), including complicated pretreatment and separation procedures, which are not only time-consuming and labor-intensive, but also incapable of simultaneously measuring both aldehydes and benzenes. In this work, a new photoionization-induced NO+ chemical ionization time-of-flight mass spectrometry (PNCI-TOFMS) was developed for real-time and continuous measurement of aldehydes and benzenes in vehicles. High-intensity NO+ reactant ions could be generated by photoionization of NO reagent gas, and efficient chemical ionization between NO+ reactant ions and analyte molecules occurred to produce adduct ions M·NO+ at an elevated ion source pressure of 800 Pa. Consequently, the achieved LODs for aldehydes and benzenes were down to sub-ppbv within 60 s. The analytical capacity of this system was demonstrated by continuous and online monitoring of in-vehicle VOCs in a used car, exhibiting broad potential applications of the PNCI-TOFMS in air pollutants monitoring and in-vehicle air quality analysis.


Assuntos
Poluentes Atmosféricos , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , Aldeídos , Benzeno , Cromatografia Gasosa-Espectrometria de Massas , Compostos Orgânicos Voláteis/análise
5.
J Agric Food Chem ; 69(36): 10496-10505, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34488337

RESUMO

Lipid peroxidation is a common event during aluminum (Al) toxicity in plants, and it generates an array of aldehyde fragments. The present study investigated and compared the profile and physiological functions of lipid peroxide-derived aldehydes under Al stress in two wheat genotypes that differed in Al resistance. Under Al stress, the sensitive genotype Yangmai-5 suffered more severe plasma membrane damage and accumulated higher levels of aldehydes in roots than the Al-tolerant genotype Jian-864. The complementary use of high-resolution mass spectrometry and standard compounds allowed the identification and quantification of 13 kinds of short-chain aldehydes sourced from lipids in wheat roots. Among these aldehydes, acetaldehyde, isovaldehyde, valeraldehyde, (E)-2-hexenal (HE), heptaldehyde, and nonyl aldehyde were the predominant species. Moreover, it was found that HE in the sensitive genotype was over 2.63 times higher than that in the tolerant genotype after Al treatment. Elimination of aldehydes using carnosine rescued root growth inhibition by 19.59 and 11.63% in Jian-864 and Yangmai-5, respectively, and alleviated Al-induced membrane damage and protein oxidation. Exogenous aldehyde application further inhibited root elongation and exacerbated oxidative injury. The tolerant genotype Jian-864 showed elevated aldehyde detoxifying enzyme activity and transcript levels. These results suggest that lipid peroxide-derived short-chain aldehydes are involved in Al toxicity, and a higher aldehyde-detoxifying capacity may be responsible for Al tolerance.


Assuntos
Alumínio , Triticum , Aldeídos/toxicidade , Alumínio/toxicidade , Peróxidos Lipídicos , Raízes de Plantas/genética , Triticum/genética
6.
Nat Commun ; 12(1): 5279, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489434

RESUMO

Chiral bridged [2,2,1] bicyclic lactones are privileged structural units in pharmaceutics and bioactive nature products. However, the synthetic methods for these compounds are rare. Here we report an efficient method for enantioselective construction of bridged [2,2,1] bicyclic lactones bearing a quaternary stereocenter via Rh-catalyzed asymmetric hydroformylation/intramolecular cyclization/pyridium chlorochromate (PCC) oxidation. By employing a hybrid phosphine-phosphite chiral ligand, a series of cyclopent-3-en-1-ols are transformed into corresponding γ-hydroxyl aldehydes with specific syn-selectivity. Then, hemiacetals form in situ and oxidation with PCC in one-pot affords bridged [2,2,1] bicyclic lactones in high yields and excellent enantiomeric excess. Replacing the hydroxyl group by an ester group, cyclopentanecarbaldehydes with a chiral all-carbon quaternary stereocenter in the γ-position can be generated efficiently.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Formiatos/química , Lactonas/síntese química , Fenazopiridina/química , Água/química , Aldeídos/química , Ciclização , Ciclopentanos/química , Humanos , Oxirredução , Fosfinas/química , Fosfitos/química , Estereoisomerismo
7.
J Agric Food Chem ; 69(39): 11665-11675, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34469152

RESUMO

The use of combinations of aroma compounds is common in many food and cosmetic applications. To investigate the binding behavior between high-amylose maize starch and binary aroma combinations of decanal and thymol, starch-aroma inclusion complexes (ICs) were prepared by a one-step or two-step method with different concentrations and orders of addition. The thymol molecule induced the starch chain to form a larger helical cavity and was more likely to form hydrogen bonds with solvents. The encapsulation efficiency and loading efficiency of starch-thymol ICs were always higher than those of starch-decanal ICs, independent of the aroma concentration and addition order in binary aroma ICs. However, starch-decanal ICs prepared in the presence of thymol encapsulated more decanal than in the absence of thymol. The V6I-type crystals formed by starch-decanal ICs and the V6III-type crystals formed by starch-thymol ICs were both present in binary aroma ICs, resulting in a less-ordered structure and lower thermal transition temperatures. In summary, the complexation between binary aroma compounds and starch exhibited both cooperative and competitive binding behaviors. The synergistic effects between decanal and thymol provide guidance in enhancing the aroma encapsulation in starch carriers.


Assuntos
Amilose , Amido , Aldeídos , Odorantes/análise , Timol
8.
Food Res Int ; 147: 110559, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34399536

RESUMO

Aldehydes and ketones are secondary oxidation products resulting from lipid oxidation that occurs during food processing. These small molecule compounds not only have an impact on the quality, odor and flavor of food, but also play a role in the pathogenesis of many human diseases. In this study, a HPLC-MS/MS analytical method was developed and validated for the simultaneous determination of 24 aldehydes and ketones. The coefficients of determination (R2) for all aldehydes and ketones were higher than 0.9975 at the range of 0.2-2000 ng/mL. The recoveries were in the range 71.20-108.13% with RSD < 10%. The method was tested by analyzing lipids from oysters with different thermal processing (boiling, frying, roasting and air frying) procedures; the highest concentration for saturated aldehydes and ketones while the highest content of unsaturated aldehydes in boiling treatment. Meanwhile, fatty acid oxidative decomposition was in agreement with aldehydes and ketones formation. Moreover, principal component analysis, orthogonal partial least-squares discriminant analysis and variable importance in projection value showed that lipid oxidation is positively related to the formation of a variety of aldehydes and ketones.


Assuntos
Aldeídos , Crassostrea , Animais , Cromatografia Líquida de Alta Pressão , Humanos , Cetonas , Espectrometria de Massas em Tandem
9.
Int J Mol Sci ; 22(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34445372

RESUMO

The synthesis of ester compounds is one of the most important chemical processes. In this work, Zn-Mg-Al mixed oxides with different Zn2+/Mg2+ molar ratios were prepared via co-precipitation method and supported gold nanoclusters to study the direct oxidative esterification of aldehyde and alcohol in the presence of molecular oxygen. Various characterization techniques such as N2-physical adsorption, X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and CO2 temperature programmed desorption (TPD) were utilized to analyze the structural and electronic properties. Based on the results, the presence of small amounts of Zn2+ ions (~5 wt.%) provoked a remarkable modification of the binary Mg-Al system, which enhanced the interaction between gold with the support and reduced the particle size of gold. For oxidative esterification reaction, the Au25/Zn0.05MgAl-400 catalyst showed the best performance, with the highest turnover frequency (TOF) of 1933 h-1. The active center was believed to be located at the interface between metallic gold with the support, where basic sites contribute a lot to transformation of the substrate.


Assuntos
Aldeídos/química , Hidróxido de Alumínio/química , Ouro/química , Hidróxido de Magnésio/química , Óxidos/química , Esterificação , Nanopartículas Metálicas , Microscopia Eletrônica de Transmissão , Oxirredução , Estresse Oxidativo , Tamanho da Partícula , Difração de Raios X , Zinco
10.
Int J Mol Sci ; 22(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34445535

RESUMO

Apples (Malus domestica Borkh) are prone to preharvest fruit drop, which is more pronounced in 'Honeycrisp'. Hexanal is known to improve fruit retention in several economically important crops. The effects of hexanal on the fruit retention of 'Honeycrisp' apples were assessed using physiological, biochemical, and transcriptomic approaches. Fruit retention and fruit firmness were significantly improved by hexanal, while sugars and fresh weight did not show a significant change in response to hexanal treatment. At commercial maturity, abscisic acid and melatonin levels were significantly lower in the treated fruit abscission zone (FAZ) compared to control. At this stage, a total of 726 differentially expressed genes (DEGs) were identified between treated and control FAZ. Functional classification of the DEGs showed that hexanal downregulated ethylene biosynthesis genes, such as S-adenosylmethionine synthase (SAM2) and 1-aminocyclopropane-1-carboxylic acid oxidases (ACO3, ACO4, and ACO4-like), while it upregulated the receptor genes ETR2 and ERS1. Genes related to ABA biosynthesis (FDPS and CLE25) were also downregulated. On the contrary, key genes involved in gibberellic acid biosynthesis (GA20OX-like and KO) were upregulated. Further, hexanal downregulated the expression of genes related to cell wall degrading enzymes, such as polygalacturonase (PG1), glucanases (endo-ß-1,4-glucanase), and expansins (EXPA1-like, EXPA6, EXPA8, EXPA10-like, EXPA16-like). Our findings reveal that hexanal reduced the sensitivity of FAZ cells to ethylene and ABA. Simultaneously, hexanal maintained the cell wall integrity of FAZ cells by regulating genes involved in cell wall modifications. Thus, delayed fruit abscission by hexanal is most likely achieved by minimizing ABA through an ethylene-dependent mechanism.


Assuntos
Ácido Abscísico/metabolismo , Aldeídos/farmacologia , Parede Celular/metabolismo , Frutas/crescimento & desenvolvimento , Malus/crescimento & desenvolvimento , Melatonina/metabolismo , Proteínas de Plantas/metabolismo , Frutas/efeitos dos fármacos , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Malus/efeitos dos fármacos , Malus/metabolismo , Proteínas de Plantas/genética
11.
Georgian Med News ; (315): 185-189, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34365448

RESUMO

The aim of this study was to obtain a more stable and less allergic form of bromelain, an enzyme complex derived from the stem of Pineapple plant (Ananas comosus L. Merr.), via chemical modification with a polysaccharide. In order to obtain purified bromelain (enriched with protein) from comercial bromelain, protein precipitation method by alcohol was used. According to our results the protein concentration after the purification was increased by about 20%. In this work, we examine the method of bromelain's chemical modification with a water-soluble, biocompatible and biodegradable natural polysaccharide - dextran, oxidized to dextran aldehyde. For the determination of the degree of bonding gel-filtration of bromelain and modified bromelain on sephadex G-75 was performed. After gel filtration of bromelain only one fraction-peak was obtained, whereas after gel filtration of modified bromelain with dextran two fraction-peaks were obtained and the degree of protein bonding with dextran was 65±5%. The method was developed both with and without the addition of cysteine. The addition of cysteine increased the activity of modified bromelain from 50±5% to 70±5%. the pH optimum for native bromelain was 7.5, whereas for modified bromelain it was shifted towards 8.5, while the temperature optimum in both cases was 60˚C. Taking into consideration the obtained results and comparing them with literary data we suggest that modified bromelain will have much potential in medical application than currently available native product. Further research is required to test the effect of this modification on bromelain's specific pharmacological and allergic properties.


Assuntos
Ananas , Bromelaínas , Aldeídos , Dextranos
12.
Mol Cell Biol ; 41(10): e0035221, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34370553

RESUMO

Sjögren-Larsson syndrome (SLS) is an inherited neurocutaneous disorder whose causative gene encodes the fatty aldehyde dehydrogenase ALDH3A2. To date, the detailed molecular mechanism of the skin pathology of SLS has remained largely unclear. We generated double-knockout (DKO) mice for Aldh3a2 and its homolog Aldh3b2 (a pseudogene in humans). These mice showed hyperkeratosis and reduced fatty aldehyde dehydrogenase activity and skin barrier function. The levels of ω-O-acylceramides (acylceramides), which are specialized ceramides essential for skin barrier function, in the epidermis of DKO mice were about 60% of those in wild-type mice. In the DKO mice, levels of acylceramide precursors (ω-hydroxy ceramides and triglycerides) were increased, suggesting that the final step of acylceramide production was inhibited. A decrease in acylceramide levels was also observed in human immortalized keratinocytes lacking ALDH3A2. Differentiated keratinocytes prepared from the DKO mice exhibited impaired long-chain base metabolism. Based on these results, we propose that the long-chain-base-derived fatty aldehydes that accumulate in DKO mice and SLS patients attack and inhibit the enzyme involved in the final step of acylceramide production. Our findings provide insight into the pathogenesis of the skin symptoms of SLS, i.e., decreased acylceramide production, and its molecular mechanism.


Assuntos
Aldeído Desidrogenase/metabolismo , Síndrome de Sjogren-Larsson/metabolismo , Pele/metabolismo , Aldeído Desidrogenase/genética , Aldeído Oxirredutases/genética , Aldeído Oxirredutases/metabolismo , Aldeídos/metabolismo , Animais , Diferenciação Celular , Ceramidas/metabolismo , Ceramidas/fisiologia , Modelos Animais de Doenças , Epiderme/metabolismo , Epiderme/fisiopatologia , Ácidos Graxos/genética , Ácidos Graxos/metabolismo , Feminino , Queratinócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Síndrome de Sjogren-Larsson/fisiopatologia
13.
Molecules ; 26(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34443627

RESUMO

The importance of yeast old yellow enzymes is increasingly recognized for direct asymmetric reduction of (E/Z)-citral to (R)-citronellal. As one of the most performing old yellow enzymes, the enzyme OYE3 from Saccharomyces cerevisiae S288C exhibited complementary enantioselectivity for the reduction of (E)-citral and (Z)-citral, resulting in lower e.e. value of (R)-citronellal in the reduction of (E/Z)-citral. To develop a novel approach for the direct synthesis of enantio-pure (R)-citronellal from the reduction of (E/Z)-citral, the enzyme OYE3 was firstly modified by semi-rational design to improve its (R)-enantioselectivity. The OYE3 variants W116A and S296F showed strict (R)-enantioselectivity in the reduction of (E)-citral, and significantly reversed the (S)-enantioselectivity in the reduction of (Z)-citral. Next, the double substitution of OYE3 led to the unique variant S296F/W116G, which exhibited strict (R)-enantioselectivity in the reduction of (E)-citral and (E/Z)-citral, but was not active on (Z)-citral. Relying on its capability discriminating (E)-citral and (Z)-citral, a new cascade reaction catalyzed by the OYE3 variant S296F/W116G and glucose dehydrogenase was developed, providing the enantio-pure (R)-citronellal and the retained (Z)-citral after complete reduction of (E)-citral.


Assuntos
Monoterpenos Acíclicos/metabolismo , NADPH Desidrogenase/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimologia , Aldeídos/metabolismo , Catálise , Glucose 1-Desidrogenase/metabolismo
14.
Int J Mol Sci ; 22(16)2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34445749

RESUMO

Cigarette smoking and alcohol consumption are major risk factors for lifestyle-related diseases. Although it has been reported that the combination of these habits worsens risks, the underlying mechanism remains elusive. Reactive carbonyl species (RCS) cause chemical modifications of biological molecules, leading to alterations in cellular signaling pathways, and total RCS levels have been used as a lipid peroxidation marker linked to lifestyle-related diseases. In this study, at least 41 types of RCS were identified in the lipophilic fraction of plasma samples from 40 subjects using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). Higher levels of 10 alkanals, 5 trans-2-alkenals, 1 cis-4-alkenal, and 3 alkadienals were detected in the smoking/drinking group (N = 10) as compared to those with either habit (N = 10 each) or without both habits (N = 10) in the analysis of covariances adjusted for age and BMI. The levels of 3 alkanals, 1 trans-2-alkenal, 1 alkadienal, and 1 4-hydroxy-2-alkenal in the smoking/drinking group were significantly higher than those in the no-smoking/drinking and no-smoking/no-drinking groups. These results strongly indicate that the combination of cigarette smoking and alcohol drinking synergistically increases the level and variety of RCS in the circulating blood, and may further jeopardize cellular function.


Assuntos
Consumo de Bebidas Alcoólicas/sangue , Aldeídos/sangue , Fumar Cigarros/sangue , Cetonas/sangue , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Cromatografia Líquida , Fumar Cigarros/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Carbonilação Proteica , Espectrometria de Massas por Ionização por Electrospray
15.
Biomolecules ; 11(8)2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34439805

RESUMO

Three novel 2-aminopyrazine Schiff bases derived from salicylaldehyde derivatives and their uranyl complexes were synthesized and characterized by elemental analysis, UV-vis, FTIR, molar conductance, and thermal gravimetric analysis (TGA). The proposed structures were optimized using density functional theory (DFT/B3LYP) and 6-311G ∗(d,p) basis sets. All uranyl complexes are soluble in DMSO and have low molar conductance, which indicates that all the complexes are nonelectrolytes. The DNA binding of those Schiff bases and their uranyl complexes was studied using UV-vis spectroscopy, and screening of their ability to bind to calf thymus DNA (CT-DNA) showed that the complexes interact with CT-DNA through an intercalation mode, for which the Kb values ranged from 1 × 106 to 3.33 × 105 M-1. The anticancer activities of the Schiff base ligands and their uranyl complexes against two ovarian (Ovcar-3) and melanoma cell lines (M14) were investigated, and the results indicated that uranyl complexes exhibit better results than the Schiff base ligands. Molecular docking identified the distance, energy account, type, and position of links contributing to the interactions between these complexes and two different cancer proteins (3W2S and 2OPZ).


Assuntos
Antineoplásicos/síntese química , Complexos de Coordenação/síntese química , Substâncias Intercalantes/síntese química , Bases de Schiff/síntese química , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/química , Aldeídos/química , Animais , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Sítios de Ligação , Bovinos , Linhagem Celular Tumoral , Complexos de Coordenação/metabolismo , Complexos de Coordenação/farmacologia , DNA/química , DNA/metabolismo , Teoria da Densidade Funcional , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Receptores ErbB/química , Receptores ErbB/metabolismo , Humanos , Concentração Inibidora 50 , Substâncias Intercalantes/metabolismo , Substâncias Intercalantes/farmacologia , Cinética , Simulação de Acoplamento Molecular , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Pirazinas/química , Bases de Schiff/metabolismo , Bases de Schiff/farmacologia , Solubilidade , Compostos de Urânio/química , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo
16.
J Med Chem ; 64(15): 11267-11287, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34288674

RESUMO

Cysteine proteases comprise an important class of drug targets, especially for infectious diseases such as Chagas disease (cruzain) and COVID-19 (3CL protease, cathepsin L). Peptide aldehydes have proven to be potent inhibitors for all of these proteases. However, the intrinsic, high electrophilicity of the aldehyde group is associated with safety concerns and metabolic instability, limiting the use of aldehyde inhibitors as drugs. We have developed a novel class of self-masked aldehyde inhibitors (SMAIs) for cruzain, the major cysteine protease of the causative agent of Chagas disease-Trypanosoma cruzi. These SMAIs exerted potent, reversible inhibition of cruzain (Ki* = 18-350 nM) while apparently protecting the free aldehyde in cell-based assays. We synthesized prodrugs of the SMAIs that could potentially improve their pharmacokinetic properties. We also elucidated the kinetic and chemical mechanism of SMAIs and applied this strategy to the design of anti-SARS-CoV-2 inhibitors.


Assuntos
Aldeídos/química , COVID-19/tratamento farmacológico , Doença de Chagas/tratamento farmacológico , Inibidores de Cisteína Proteinase/uso terapêutico , SARS-CoV-2/enzimologia , Trypanosoma cruzi/enzimologia , Aldeídos/metabolismo , Aldeídos/farmacologia , Catepsina L/antagonistas & inibidores , Catepsina L/metabolismo , Cisteína Endopeptidases/metabolismo , Cisteína Proteases/metabolismo , Inibidores de Cisteína Proteinase/química , Desenho de Fármacos , Humanos , Cinética , Modelos Moleculares , Estrutura Molecular , Proteínas de Protozoários/antagonistas & inibidores , Proteínas de Protozoários/metabolismo , SARS-CoV-2/efeitos dos fármacos , Relação Estrutura-Atividade , Trypanosoma cruzi/efeitos dos fármacos
17.
Chemosphere ; 281: 130996, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34289634

RESUMO

As one of the main components of combustion of tobacco products occurs (CARB), crotonaldehyde has an acute toxicity and widely exists in the atmosphere, which is harmful to human health. The removal efficiency of VOCs by ozonation can reach 80-90%. Based on the theory of quantum chemistry, the degradation mechanism, kinetics and toxicity of crotonaldehyde by ozonation in gas phase and heterogeneous phase were studied. Ozone was added to the olefins unsaturated double bond to form a five-membered ring primary ozonide, which was further fractured due to its unstable structure to form a Criegee intermediate and an aldehyde compound. The reaction rate constant of crotonaldehyde with ozone was 1.24 × 10-17 cm3 molecule-1 s-1 at 298 K and 1 atm, which was an order of magnitude higher than the experimental value. From toxicity assessment, it was found that the ozonation of crotonaldehyde is beneficial to the removal of toxicity. Mineral dust aerosol exists in the atmosphere in large quantities, and SiO2 is the most abundant component. VOCs are transformed into particle state on their surface through homogeneous nucleation and heterogeneous nucleation. Referring to the crystal structure of SiO2, five hydroxylated silica oligomer cluster structures were simulated and the adsorption configurations of crotonaldehyde on their surface were simulated. The adsorption of crotonaldehyde on the surface of the clusters was achieved by forming hydrogen bonds and had good adsorption effects. The adsorption of hydroxylated silica oligomer clusters didn't change the ozonation mechanism of crotonldehyde, but had a certain effect on the reaction rate.


Assuntos
Ozônio , Dióxido de Silício , Adsorção , Aldeídos , Humanos
18.
Rinsho Ketsueki ; 62(6): 547-553, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34219079

RESUMO

We have recently described the identification of a novel inherited bone marrow failure syndrome. The first set of patients was diagnosed through the exome analysis of cells from Japanese patients with hypoplastic anemia, which have been deposited to the JCRB cell bank for quite some time previously. Originally, these cases were diagnosed with a novel disorder based on increased levels of sister chromatid exchanges in lymphocytes; however, causative genes were clarified only after applying the recently developed next-generation sequencing technology. Aldehyde degradation deficiency syndrome (ADDS) is caused by combined defects in two genes, ADH5 and ALDH2, which are both critical for degrading endogenously generated formaldehyde. Formaldehyde is highly reactive and toxic to biological molecules including DNA, and its endogenous generation in the absence of the degradation system results in DNA damage that overwhelms the DNA repair capacity, leading to the development of BMF with loss of hematopoietic stem cells and progression to MDS/leukemia. In this short review, we would like to summarize what is known today about ADDS for a wide readership of hematology clinicians in Japan.


Assuntos
Anemia de Fanconi , Proteínas Adaptadoras de Transdução de Sinal , Álcool Desidrogenase , Aldeído-Desidrogenase Mitocondrial/metabolismo , Aldeídos , Síndrome Congênita de Insuficiência da Medula Óssea , Humanos , Japão
19.
Molecules ; 26(14)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34299536

RESUMO

The volatile thiol compound 3-sulfanylhexan-1-ol (3SH) is a key impact odorant of white wines such as Sauvignon Blanc. 3SH is produced during fermentation by metabolism of non-volatile precursors such as 3-S-gluthathionylhexanal (glut-3SH-al). The biogenesis of 3SH is not fully understood, and the role of glut-3SH-al in this pathway is yet to be elucidated. The aldehyde functional group of glut-3SH-al is known to make this compound more reactive than other precursors to 3SH, and we are reporting for the first time that glut-3SH-al can exist in both keto and enol forms in aqueous solutions. At wine typical pH (~3.5), glut-3SH-al exists predominantly as the enol form. The dominance of the enol form over the keto form has implications in terms of potential consumption/conversion of glut-3SH-al by previously unidentified pathways. Therefore, this work will aid in the further elucidation of the role of glut-3SH-al towards 3SH formation in wine, with significant implications for the study and analysis of analogous compounds.


Assuntos
Compostos de Enxofre/metabolismo , Aldeídos/metabolismo , Fermentação/fisiologia , Hexanóis/metabolismo , Odorantes/análise , Compostos de Sulfidrila/metabolismo , Vitis/metabolismo , Vinho/análise
20.
Talanta ; 233: 122522, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34215137

RESUMO

Aldehydes are toxic carbonyl compounds that are identified in various matrices surrounding us. For instance, aldehydes could be formed during the cooking and frying of foods which affects the food quality and safety. Derivatization is a must for the determination of aldehydes as they lack intrinsic chromophoric groups. 2,4-Dinitrophenyl hydrazine (DNPH) is the most used derivatizing reagent for aldehydes and the formed hydrazones could be determined by either HPLC-UV or LC-MS. However, UV detection is non-sensitive, and the MS equipment is expensive and not widely available. Thus, herein we report a smart chemiluminescence (CL) detection method for the DNPH aldehydes derivatives. These derivatives are supposed to possess photosensitization ability due to the presence of strong chromophoric structures; nitrobenzene and phenyl hydrazone. Upon their UV irradiation, singlet oxygen is found to be produced which then converts the DNPH-aldehyde derivative into hydroperoxide. Next, the hydroperoxide reacts with luminol in an alkaline medium producing a strong CL. An HPLC system with online UV irradiation and online reaction with luminol followed by CL detection was constructed and used for the determination of aldehydes after their derivatization with DNPH. The developed method showed excellent sensitivity with detection limits down to 1.5-18.5 nM. The achieved sensitivity is superior to that obtained by HPLC-UV and LC-MS detection methods for DNPH-aldehydes derivatives. Additionally, our approach is an chemiluminogenic where the DNPH reagent itself does not produce CL which is an excellent advantage. The method was applied successfully for the determination of aldehydes in canola oil samples using simple liquid-liquid extraction showing good recovery (87.0-106.0%), accuracy (87.2-106.6), and precision (RSD≤10.2%). After analysis of fresh and heated oil samples, it was demonstrated that heating of oil, even for short time, strongly elevated the level of their aldehydes' content. At last, it was found that the results of the analysis of aldehydes in oil samples using the proposed method perfectly matched those obtained by a reference LC-MS method.


Assuntos
Aldeídos , Luminol , Cromatografia Líquida de Alta Pressão , Hidrazinas , Luminescência , Fenil-Hidrazinas
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