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1.
J Environ Sci (China) ; 148: 27-37, 2025 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39095163

RESUMO

Naphthenic acids, NAs, are a major contaminant of concern and a focus of much research around remediation of oil sand process affected waters, OSPW. Using activated carbon adsorbents are an attractive option given their low cost of fabrication and implementation. A deeper evaluation of the effect NA structural differences have on uptake affinity is warranted. Here we provide an in-depth exploration of NA adsorption including many more model NA species than have been assessed previously with evaluation of adsorption kinetics and isotherms at the relevant alkaline pH of OSPW using several different carbon adsorbents with pH buffering to simulate the behaviour of real OSPW. Uptake for the NA varied considerably regardless of the activated carbon used, ranging from 350 mg/g to near zero highlighting recalcitrant NAs. The equilibrium data was explored to identify structural features of these species and key physiochemical properties that influence adsorption. We found that certain NA will be resistant to adsorption when hydrophobic adsorbents are used. Adsorption isotherm modelling helped explore interactions occurring at the interface between NA and adsorbent surfaces. We identified the importance of NA hydrophobicity for activated carbon uptake. Evidence is also presented that indicates favorable hydrogen bonding between certain NA and surface site hydroxyl groups, demonstrating the importance of adsorbent surface functionality for NA uptake. This research highlights the challenges associated with removing NAs from OSPW through adsorption and also identifies how adsorbent surface chemistry modification can be used to increase the removal efficiency of recalcitrant NA species.


Assuntos
Ácidos Carboxílicos , Poluentes Químicos da Água , Adsorção , Ácidos Carboxílicos/química , Poluentes Químicos da Água/química , Carvão Vegetal/química , Modelos Químicos , Cinética , Concentração de Íons de Hidrogênio
2.
J Med Chem ; 67(17): 15456-15475, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39225755

RESUMO

DNA N6-methyladenine (6mA) demethylase ALKBH1 plays an important role in various cellular processes. Dysregulation of ALKBH1 is associated with the development of some cancer types, including gastric cancer, implicating a potential therapeutic target. However, there is still a lack of potent ALKBH1 inhibitors. Herein, we report the discovery of a highly potent ALKBH1 inhibitor, 1H-pyrazole-4-carboxylic acid derivative 29. The structure-activity relationship of this series of compounds was also discussed. Because of the poor cell membrane permeability of 29, we prepared a prodrug of 29 (29E), which showed excellent cellular activities. In gastric cancer cell lines HGC27 and AGS, 29E treatment significantly increased the abundance of 6mA, inhibited cell viability, and upregulated the AMP-activated protein kinase (AMPK) signaling pathway. In addition, the hydrolysis product 29 showed high exposure in mice after administration of 29E. Collectively, this research provides a new potent ALKBH1 inhibitor, which could serve as a lead compound for subsequent drug development.


Assuntos
Homólogo AlkB 1 da Histona H2a Dioxigenase , Antineoplásicos , Inibidores Enzimáticos , Pirazóis , Neoplasias Gástricas , Humanos , Relação Estrutura-Atividade , Homólogo AlkB 1 da Histona H2a Dioxigenase/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Animais , Pirazóis/farmacologia , Pirazóis/química , Pirazóis/síntese química , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Linhagem Celular Tumoral , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacologia , Ácidos Carboxílicos/síntese química , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Simulação de Acoplamento Molecular , Camundongos Nus , Camundongos Endogâmicos BALB C
3.
J Biosci Bioeng ; 138(4): 283-289, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39097441

RESUMO

GroEL, a chaperone protein responsible for peptide and denatured protein folding, undergoes substantial conformational changes driven by ATP binding and hydrolysis during folding. Utilizing these conformational changes, we demonstrated the GroEL-mediated regioselective photocyclodimerization of 2-anthracenecarboxylic acid (AC) using ATP hydrolysis as an external stimulus. We designed and prepared an optimal GroEL mutant to employ in a docking simulation that has been actively used in recent years. Based on the large difference in the motif of hydrogen bonds between AC and GroEL mutant compared with the wild-type, we predicted that GroELMEL, in which the 307‒309th amino acid residues were mutated to Ala, could alter the orientation of bound AC in GroEL. The GroELMEL-mediated photocyclodimerization of AC can be used for regioselective inversion upon ATP addition to a moderate extent.


Assuntos
Trifosfato de Adenosina , Antracenos , Chaperonina 60 , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/química , Hidrólise , Antracenos/química , Antracenos/metabolismo , Chaperonina 60/química , Chaperonina 60/genética , Chaperonina 60/metabolismo , Simulação de Acoplamento Molecular , Conformação Proteica , Mutação , Ligação de Hidrogênio , Dobramento de Proteína , Ácidos Carboxílicos
4.
J Am Soc Mass Spectrom ; 35(9): 2041-2055, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39140654

RESUMO

In this investigation, we detail the synthesis of silver nanoparticles (AgNPs) via a precise chemical vacuum deposition (CVD) methodology, aimed at augmenting the analytical performance of laser desorption/ionization mass spectrometry (LDI-MS) for the detection of low-molecular-weight analytes. Employing a precursor supply rate of 0.0014 mg/s facilitated the formation of uniformly dispersed AgNPs, characterized by SEM and AFM to have an average diameter of 33.5 ± 1.5 nm and a surface roughness (Ra) of 11.8 nm, indicative of their homogeneous coverage and spherical morphology. XPS and SEM-EDX analyses confirmed the metallic silver composition of the nanoparticles with Ag peak splitting, reflecting the successful synthesis of metallic Ag. Comparative analytical evaluation with traditional MALDI matrices revealed that AgNPs significantly reduce signal suppression, thereby enhancing the sensitivity and specificity of LDI-MS for low-molecular-weight compounds such as triglycerides, saccharides, amino acids, and carboxylic acids. Notably, the application of AgNPs demonstrated a superior linear response for triglyceride signals with regression coefficients surpassing 0.99, markedly outperforming conventional matrices. The study further extends into quantitative analysis through nanoparticle-based laser desorption/ionization (NALDI), where AgNPs exhibited enhanced ionization efficiency, characterized by substantially lower limits of detection (LOD) and quantification (LOQ) for tested standards. Particular attention was paid to lipids with a detailed examination of their fragmentation pathways. These results highlight the significant potential of AgNPs synthesized via CVD to transform the analytical detection and quantification of low-molecular-weight compounds using NALDI. This approach offers a promising avenue for expanding the scope of analytical applications in mass spectrometry and introducing innovative methodologies for enhanced precision and sensitivity.


Assuntos
Nanopartículas Metálicas , Prata , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Prata/química , Nanopartículas Metálicas/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Aminoácidos/análise , Aminoácidos/química , Peso Molecular , Triglicerídeos/análise , Triglicerídeos/química , Ácidos Carboxílicos/química , Ácidos Carboxílicos/análise , Limite de Detecção
5.
Org Biomol Chem ; 22(34): 6999-7005, 2024 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-39118586

RESUMO

Despite the remarkable developments of the Ugi reaction and its variants, the use of ammonia in the Ugi reaction has long been recognized as impractical and unsuccessful. Indeed, the ammonia-Ugi reaction often requires harsh reaction conditions, such as heating and microwave irradiation, and competes with the Passerini reaction, thereby resulting in low yields. This study describes a robust and practical ammonia-Ugi reaction protocol. Using originally prepared ammonium carboxylates in trifluoroethanol, the ammonia-Ugi reaction proceeded at room temperature in high yields and showed a broad substrate scope, thus synthesizing a variety of α,α-disubstituted amino acid derivatives, including unnatural dipeptides. The reaction required no condensing agents and proceeded without racemization of the chiral stereocenter of α-amino acids. Furthermore, using this protocol, we quickly synthesized a novel dipeptide, D-Leu-Aic-NH-CH2Ph(p-F), which exhibited a potent inhibitory activity against α-chymotrypsin with a Ki value of 0.091 µM.


Assuntos
Aminoácidos , Amônia , Dipeptídeos , Dipeptídeos/química , Dipeptídeos/síntese química , Amônia/química , Aminoácidos/química , Aminoácidos/síntese química , Ácidos Carboxílicos/química , Ácidos Carboxílicos/síntese química , Compostos de Amônio/química , Quimotripsina/antagonistas & inibidores , Quimotripsina/química , Estrutura Molecular , Técnicas de Química Sintética
6.
Int J Mol Sci ; 25(15)2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39125926

RESUMO

Hollongdione is the first recorded example of the occurrence of a dammarane hexanor-triterpene in nature possessing antiviral and cytotoxic activity. Its simple one-stage transformation into compounds with terminal alkyne and vinyl chloride fragments via the interaction with phosphorus halides is reported. The copper(I)-catalyzed Mannich reaction of 3-oxo-22,23,24,25,26,27-hexanor-dammar-20(21)-in 3 led to a series of aminomethylated products, while 17-carboxylic acid was obtained by ozone oxidation of 3-oxo-22,23,24,25,26,27-hexanor-dammar-20-chloro-20(21)-en 4; the following direct amidation of the latter has been developed. The structures of all new molecules were established by spectroscopic studies that included 2D NMR correlation methods; the molecular structures of compounds 2-5 were determined by X-ray analysis.


Assuntos
Alcinos , Ácidos Carboxílicos , Bases de Mannich , Cloreto de Vinil , Alcinos/química , Ácidos Carboxílicos/química , Bases de Mannich/química , Cloreto de Vinil/química , Triterpenos/química , Estrutura Molecular , Catálise , Espectroscopia de Ressonância Magnética
7.
Antimicrob Agents Chemother ; 68(9): e0075124, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39133021

RESUMO

Taniborbactam, a bicyclic boronate ß-lactamase inhibitor with activity against Klebsiella pneumoniae carbapenemase (KPC), Verona integron-encoded metallo-ß-lactamase (VIM), New Delhi metallo-ß-lactamase (NDM), extended-spectrum beta-lactamases (ESBLs), OXA-48, and AmpC ß-lactamases, is under clinical development in combination with cefepime. Susceptibility of 200 previously characterized carbapenem-resistant K. pneumoniae and 197 multidrug-resistant (MDR) Pseudomonas aeruginosa to cefepime-taniborbactam and comparators was determined by broth microdilution. For K. pneumoniae (192 KPC; 7 OXA-48-related), MIC90 values of ß-lactam components for cefepime-taniborbactam, ceftazidime-avibactam, and meropenem-vaborbactam were 2, 2, and 1 mg/L, respectively. For cefepime-taniborbactam, 100% and 99.5% of isolates of K. pneumoniae were inhibited at ≤16 mg/L and ≤8 mg/L, respectively, while 98.0% and 95.5% of isolates were susceptible to ceftazidime-avibactam and meropenem-vaborbactam, respectively. For P. aeruginosa, MIC90 values of ß-lactam components of cefepime-taniborbactam, ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam were 16, >8, >8, and >4 mg/L, respectively. Of 89 carbapenem-susceptible isolates, 100% were susceptible to ceftolozane-tazobactam, ceftazidime-avibactam, and cefepime-taniborbactam at ≤8 mg/L. Of 73 carbapenem-intermediate/resistant P. aeruginosa isolates without carbapenemases, 87.7% were susceptible to ceftolozane-tazobactam, 79.5% to ceftazidime-avibactam, and 95.9% and 83.6% to cefepime-taniborbactam at ≤16 mg/L and ≤8 mg/L, respectively. Cefepime-taniborbactam at ≤16 mg/L and ≤8 mg/L, respectively, was active against 73.3% and 46.7% of 15 VIM- and 60.0% and 35.0% of 20 KPC-producing P. aeruginosa isolates. Of all 108 carbapenem-intermediate/resistant P. aeruginosa isolates, cefepime-taniborbactam was active against 86.1% and 69.4% at ≤16 mg/L and ≤8 mg/L, respectively, compared to 59.3% for ceftolozane-tazobactam and 63.0% for ceftazidime-avibactam. Cefepime-taniborbactam had in vitro activity comparable to ceftazidime-avibactam and greater than meropenem-vaborbactam against carbapenem-resistant K. pneumoniae and carbapenem-intermediate/resistant MDR P. aeruginosa.


Assuntos
Antibacterianos , Cefepima , Farmacorresistência Bacteriana Múltipla , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa , Inibidores de beta-Lactamases , Cefepima/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Antibacterianos/farmacologia , Inibidores de beta-Lactamases/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Cefalosporinas/farmacologia , Humanos , beta-Lactamases/metabolismo , beta-Lactamases/genética , Ácidos Borônicos/farmacologia , Carbapenêmicos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Ceftazidima/farmacologia , Ácidos Borínicos/farmacologia , Combinação de Medicamentos , Compostos Azabicíclicos/farmacologia , Ácidos Carboxílicos
8.
Inorg Chem ; 63(33): 15421-15432, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39115163

RESUMO

The escalating levels of hazardous pharmaceutical contaminants, specifically nonsteroidal anti-inflammatory drugs (NSAIDs), in groundwater reservoir surfaces and surface waterway systems have prompted substantial scientific interest regarding their potential deleterious effects on both aquatic ecosystems and human health. Extraction of those pollutants from wastewater is quite challenging. Hence, the development of economic, sustainable, and scalable techniques for capturing and removing those pollutants is crucial to ensure water safety. Herein, we demonstrate a physicochemically stable, reusable, porous Hf(IV)-based cationic metal-organic framework (MOF), namely, 1'@MeCl for the aqueous phase adsorption-based removal of NSAIDs (diclofenac, naproxen, ibuprofen) from the wastewater environment. The highly positively charged surface of the 1'@MeCl MOF enables it to selectively extract more than 99% of diclofenac, naproxen, and ibuprofen contaminants within less than 30 s. With fast adsorption kinetics, very high adsorption capacities (Qe) were achieved at neutral pH for diclofenac (482.9 mg/g), naproxen (295.9 mg/g), and ibuprofen (219.5 mg/g). Moreover, the influence of changes in pH and coexisting anions on the adsorption property of the 1'@MeCl MOF was studied. Furthermore, the adsorption efficiency of 1'@MeCl in different real water environments was ensured by performing diclofenac, naproxen, and ibuprofen adsorption from tap, river, and lake water. Moreover, a 1'@MeCl-anchored cellulose acetate-chitosan membrane was developed successfully to demonstrate the membrane-based extraction of diclofenac, naproxen, and ibuprofen from contaminated water. Furthermore, a molecular-level mechanistic study was performed through experimental and computational study to propose the plausible adsorption mechanisms for diclofenac, naproxen, and ibuprofen over the surface of 1'@MeCl.


Assuntos
Anti-Inflamatórios não Esteroides , Estruturas Metalorgânicas , Poluentes Químicos da Água , Estruturas Metalorgânicas/química , Adsorção , Poluentes Químicos da Água/isolamento & purificação , Poluentes Químicos da Água/química , Concentração de Íons de Hidrogênio , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Diclofenaco/química , Diclofenaco/isolamento & purificação , Naproxeno/química , Naproxeno/isolamento & purificação , Ibuprofeno/química , Ibuprofeno/isolamento & purificação , Propriedades de Superfície , Ácidos Carboxílicos/química , Ácidos Carboxílicos/isolamento & purificação , Estrutura Molecular , Teoria da Densidade Funcional , Cátions/química
9.
Bioresour Technol ; 409: 131191, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39094964

RESUMO

Producing medium chain fatty acids (MCFAs) from waste activated sludge (WAS) is crucial for sustainable chemical industries. This study addressed the electron donor requirement for MCFAs production by inoculating Lactobacillus at varying concentrations (7.94 × 1010, 3.18 × 1011, and 6.35 × 1011 cell/L) to supply lactate internally. Interestingly, the highest MCFAs yield (∼2000 mg COD/L) occurred at the lowest Lactobacillus inoculation. Higher inoculation concentrations redirected more carbon from WAS towards alcohols production rather than MCFAs generation, with up to 2852 mg COD/L alcohols obtained under 6.35 × 1011 cell/L inoculation. Clostridium dominance and increased genes abundance for substrate hydrolysis, lactate conversion, and MCFAs/alcohol production collectively enhanced WAS-derived MCFAs and alcohols synthesis after Lactobacillus inoculation. Overall, the strategy of Lactobacillus inoculation regulated fermentation outcomes and subsequent carbon recovery in WAS, presenting a sustainable technology to achieve liquid bio-energy production from underutilized wet wastes.


Assuntos
Álcoois , Fermentação , Lactobacillus , Esgotos , Esgotos/microbiologia , Lactobacillus/metabolismo , Álcoois/metabolismo , Ácidos Carboxílicos/metabolismo , Redes e Vias Metabólicas
10.
J Med Chem ; 67(16): 13639-13665, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39096294

RESUMO

Inositol hexakisphosphate kinases (IP6Ks) have been studied for their role in glucose homeostasis, metabolic disease, fatty liver disease, chronic kidney disease, neurological development, and psychiatric disease. IP6Ks phosphorylate inositol hexakisphosphate (IP6) to the pyrophosphate, 5-diphosphoinositol-1,2,3,4,6-pentakisphosphate (5-IP7). Most of the currently known potent IP6K inhibitors contain a critical carboxylic acid which limits blood-brain barrier (BBB) penetration. In this work, the synthesis and testing of a variety of carboxylic acid isosteres resulted in several new compounds with improved BBB penetration. The most promising compound has an IP6K1 IC50 of 16 nM with an improved brain/plasma ratio and a favorable pharmacokinetic profile. This series of brain penetrant compounds may be used to investigate the role of IP6Ks in CNS disorders.


Assuntos
Barreira Hematoencefálica , Fosfotransferases (Aceptor do Grupo Fosfato) , Barreira Hematoencefálica/metabolismo , Fosfotransferases (Aceptor do Grupo Fosfato)/metabolismo , Fosfotransferases (Aceptor do Grupo Fosfato)/antagonistas & inibidores , Animais , Humanos , Relação Estrutura-Atividade , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Camundongos , Masculino , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacologia , Ácidos Carboxílicos/síntese química , Ratos
11.
Water Res ; 263: 122188, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39098152

RESUMO

Refractory naphthenic acids (NAs) are among the primary toxic compounds in oil sands process water (OSPW), a matrix with a complex chemical composition that poses challenges to its remediation. This study evaluated the effectiveness of calcium peroxide (CaO2) combined with solar radiation (solar/CaO2) as an advanced water treatment process for degrading model NAs (1,2,3,4-tetrahydronaphthalene-2-carboxylic acid, pentanoic acid, and diphenylacetic acid) in synthetic water (STW) and provide preliminary insights in treating real OSPW. Solar light and CaO2 acted synergistically to degrade target NAs in STW (>67 of synergistic factor) following a pseudo-first-order kinetic (R2 ≥ 0.95), with an optimal CaO2 dosage of 0.1 g L-1. Inorganic ions and dissolved organic matter were found to hinder the degradation of NAs by solar/CaO2 treatment; however, the complete degradation of NAs was reached in 6.7 h of treatment. The main degradation mechanism involved the generation of hydroxyl radicals (•OH), which contributed ∼90% to the apparent degradation rate constant (K), followed by H2O2 (4-5%) and 1O2 (0-5%). The tentative transformation pathways of three NAs were proposed, confirming an open-ring reaction and resulting in short-chain fatty acid ions as final products. Furthermore, a reduction in acute microbial toxicity and genotoxic effect was observed in the treated samples, suggesting that solar/CaO2 treatment exhibits high environmental compatibility. Furthermore, the solar/CaO2 system was successfully applied as a preliminary step for real-world applications to remove natural NAs, fluorophore organic compounds, and inorganic components from OSPW, demonstrating the potential use of this technology in the advanced treatment of oil-tailing-derived NAs.


Assuntos
Peróxidos , Poluentes Químicos da Água , Peróxidos/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/toxicidade , Ácidos Carboxílicos/química , Campos de Petróleo e Gás , Purificação da Água/métodos , Naftalenos/química , Luz Solar
12.
J Med Chem ; 67(16): 14062-14076, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39138970

RESUMO

Several conjugates between folic acid and a series of kinetically stable lanthanide complexes have been synthesized, using amide coupling and azide-alkyne cycloaddition methodologies to link the metal-binding domain to folate through a variety of spacer groups. While all these complexes exhibit affinity for the folate receptor, it is clear that the point of attachment to folate is essential, with linkage through the γ-carboxylic acid giving rise to significantly enhanced receptor affinity. All the conjugates studied show affinities consistent with displacing biological circulating folate derivatives, 5-methyltetrahydrofolate, from folate receptors. All the complexes exhibit luminescence with a short-lived component arising from ligand fluorescence overlaid on a much longer lived terbium-centered component. These can be separated using time-gating methods. From the results obtained, the most promising approach to achieve sensitized luminescence in these systems requires incorporating a sensitizing chromophore close to the lanthanide.


Assuntos
Ácido Fólico , Térbio , Humanos , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/metabolismo , Receptores de Folato com Âncoras de GPI/metabolismo , Ácido Fólico/química , Ácido Fólico/metabolismo , Substâncias Luminescentes/química , Substâncias Luminescentes/síntese química , Térbio/química , Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/química
13.
J Inorg Biochem ; 260: 112700, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39163715

RESUMO

The success of a classic inorganic coordination compound, Cisplatin, cis-[Pt(NH3)2Cl2], as the first anticancer metallodrug started a field of research dedicated to discovering coordination compounds with antitumor activity, encompassing various metals. Among these, copper complexes have emerged as interesting candidates to develop drugs to treat cancer. In this work, mixed ligand complexes of Cu(II) with diimines (phenanthroline or 4-methylphenanthroline) and 3-(4-hydroxyphenyl)propanoate, phenylcarboxylate or phenylacetate were synthesized. They were characterized in the solid state, including a new crystal structure of [Cu2(3-(4-hydroxyphenyl)propanoate)3(phenanthroline)2]Cl·H2O. The obtained complexes presented a variety of stoichiometries. In solution, complexes were partially dissociated in the corresponding Cu-diimine complex. The complexes bound to the DNA by partial intercalation and groove binding, as assessed by Circular Dichroism, relative viscosity change and UV-Vis titration. The cytotoxicity of the complexes was determined in vitro on MDA-MB-231, MCF-7 (human metastatic breast adenocarcinomas, the first triple negative), MCF-10A (breast nontumoral), A549 (human lung epithelial carcinoma), and MRC-5 (human nontumoral lung epithelial cells), finding an activity higher than that of Cisplatin, although with less selectivity.


Assuntos
Antineoplásicos , Complexos de Coordenação , Cobre , Fenantrolinas , Humanos , Cobre/química , Fenantrolinas/química , Fenantrolinas/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Linhagem Celular Tumoral , Ligantes , DNA/química , DNA/metabolismo , Células A549 , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Células MCF-7
14.
Chem Pharm Bull (Tokyo) ; 72(8): 767-771, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39198181

RESUMO

α-Alkoxy bridgehead radicals enable intermolecular construction of sterically congested C-C bonds due to their sterically accessible nature. We implemented these radical species into total syntheses of various densely oxygenated natural products and demonstrated their exceptional versatility. Herein, we employed different precursors to generate the same α-alkoxy bridgehead radical and compared the efficacy of the precursors for coupling reactions. Specifically, the bridgehead radical of the trioxaadamantane structure was formed from α-alkoxy carboxylic acid, selenide/telluride, and acyl selenide/acyl telluride, and reacted with 4-((tert-butyldimethylsilyl)oxy)cyclopent-2-en-1-one and 5-oxo-1-cyclopentene-1-carbonitrile. The efficiency of the bridgehead radical formation and subsequent coupling reaction significantly depended on the structures of the precursors and acceptors as well as the reaction conditions. Our findings provide new insights for selecting the appropriate substrates of key coupling reactions in the total synthesis of complex natural products.


Assuntos
Ácidos Carboxílicos , Telúrio , Ácidos Carboxílicos/química , Ácidos Carboxílicos/síntese química , Telúrio/química , Estrutura Molecular , Radicais Livres/química , Compostos de Selênio/química , Compostos de Selênio/síntese química , Compostos Organosselênicos/química , Compostos Organosselênicos/síntese química , Produtos Biológicos/química , Produtos Biológicos/síntese química
15.
Molecules ; 29(15)2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39125070

RESUMO

The COVID-19 pandemic highlighted the need to create and study new substances with improved lipophilicity and antimicrobial properties, such as ionic liquids (ILs), with easily tunable physicochemical properties. Most ILs possess strong antibacterial effects, but ILs containing the imidazolium cation are even more effective than the positive control. Thus, in this study, three ionic liquids with 1-butyl-3-methylimidazolium cation and various carboxylate anions (phenylacetate, benzoate, and 4-methoxyphenylacetate) were synthesized and fully characterized. The interactions between the cations and anions were discussed based on the experimental density, viscosity, and electrical conductivity. From the measured electrical conductivity and viscosity, the Walden plot is constructed and ionicity of the studied ILs is discussed. The similarities and dissimilarities among the studied ILs and their physicochemical properties are analyzed by applying the hierarchical cluster analysis and in silico calculated properties. The antimicrobial activity of the studied ionic liquids is tested on two bacterial (E. coli and P. aeruginosa) and three fungi (P. verrucosum, A. flavus, and A. parasiticus) strains, finding that they showed improved antimicrobial activity compared to the individual components.


Assuntos
Anti-Infecciosos , Ácidos Carboxílicos , Líquidos Iônicos , Líquidos Iônicos/química , Líquidos Iônicos/farmacologia , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/síntese química , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacologia , Viscosidade , Imidazóis/química , Imidazóis/farmacologia , Imidazóis/síntese química , Condutividade Elétrica , Testes de Sensibilidade Microbiana , Simulação por Computador , Escherichia coli/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , COVID-19/virologia
16.
Org Lett ; 26(31): 6754-6759, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39077878

RESUMO

On-DNA carboxylic acids are important synthetic intermediates in the synthesis of DNA-encoded library (DEL) structures. Herein, we report an oxoammonium salt-mediated, room temperature, solution-phase oxidation of DNA-linked primary alcohols into carboxylic acids. This method exhibits a wide substrate scope, encompassing aliphatic, benzylic, and heterobenzylic alcohols, and is compatible with DEL encoding strategies. This advancement facilitates a DEL strategy to utilize unprotected alcohols as inert, masked carboxylic acids and enables access to noncommercial bifunctional carboxyl intermediates to enhance the accessible chemical diversity within DELs.


Assuntos
Álcoois , DNA , Oxirredução , Estrutura Molecular , Álcoois/química , DNA/química , Ácidos Carboxílicos/química , Sais/química
17.
Anal Chem ; 96(32): 12937-12942, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39082755

RESUMO

Liquid chromatography-mass spectrometry (LC-MS) based metabolomics suffers from extended duty cycles and matrix-dependent quantitation. Chemical tags with 96 unique masses are reported, which alleviate the metabolomic workflow bottleneck and allow for absolute quantitation. A metabolic screen for carboxylic acids was performed on mammalian cells deprived of various nutrients and showed 24% RSD and analysis of 288 samples in 2 h.


Assuntos
Metabolômica , Metabolômica/métodos , Humanos , Espectrometria de Massas , Marcação por Isótopo , Ácidos Carboxílicos/metabolismo , Ácidos Carboxílicos/análise , Cromatografia Líquida/métodos , Ensaios de Triagem em Larga Escala
18.
Spectrochim Acta A Mol Biomol Spectrosc ; 321: 124737, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38963946

RESUMO

The molecule of 2-Biphenyl Carboxylic Acid (2BCA), which contains peculiar features, was explored making use of density functional theory (DFT) and experimental approaches in the area of quantum computational research. The optimised structure, atomic charges, vibrational frequencies, electrical properties, electrostatic potential surface (ESP), natural bond orbital analysis and potential energy surface (PES) were obtained applying the B3LYP approach with the 6-311++ G (d,p) basis set.. The 2BCA molecule was examined for possible conformers using a PES scan. The methods applied for spectral analyses included FT-IR, FT-RAMAN, NMR, and UV-Vis results. Vibrational frequencies for all typical modes of vibration were found using the Potential Energy Distribution (PED) data. The UV-Vis spectrum was simulated using the TD-DFT technique, which is also seen empirically. The Gauge-Invariant Atomic Orbital (GIAO) approach was employed to model and study the 13C and 1H NMR spectra of the 2BCA molecule in a CDCL3 solution. The spectra were then exploited experimentally to establish their chemical shifts. To predict the donor and acceptor interaction, the NBO analysis was used. The electrostatic potential surface was employed to anticipate the locations of nucleophilic and electrophilic sites. Hirshfeld surfaces and their related fingerprint plots are exploited for the investigation of intermolecular interactions. Reduced Density Gradient (RDG) helps to measure and illustrate electron correlation effects, offering precise insights into chemical bonding, reactivity, and the electronic structure of 2BCA. According to Lipinski and Veber's drug similarity criteria, 2BCA exhibits the typical physicochemical and pharmacokinetic properties that make it a potential oral pharmaceutical candidate. According to the findings of a molecular docking study, the 2BCA molecule has promise as a treatment agent for the Nipah virus (PDB ID: 6 EB9), which causes severe respiratory and neurological symptoms in humans.


Assuntos
Vírus Nipah , Análise Espectral Raman , Eletricidade Estática , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Vírus Nipah/química , Vírus Nipah/efeitos dos fármacos , Vírus Nipah/metabolismo , Análise Espectral Raman/métodos , Proteínas Virais/química , Proteínas Virais/metabolismo , Ligação Proteica , Simulação de Acoplamento Molecular , Teoria da Densidade Funcional , Espectrofotometria Ultravioleta , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Vibração , Conformação Molecular , Ácidos Carboxílicos/química
19.
Chemosphere ; 363: 142941, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39067819

RESUMO

Within the new circular economy paradigm, this work evaluates the performance of tailored mixed metal oxides (MMO) anodes, based on ruthenium and antimony, for their application into an electrochemically-assisted organic refinery process. This process is designed to transform pollutants into value-added products with minimal mineralization. Oxidation of synthetic wastes consisting of phenol solutions was used to validate the electrochemical conversion of phenolic wastes into carboxylates, which are then considered as bricks to be used for electrosynthesis or to produce fuels. The MMO anodes were manufactured using two synthesis routes (Pechini method and ionic liquid method), each followed by one of three different heating treatments: furnace, microwave, and CO2 laser. The selection of the optimal electrode for the organic electrorefinery was based on a combination of physical and electrochemical properties, degradation performance of phenol to carboxylates, and long-term stability, looking for a truly sustainable solution. Results indicate that anodes synthesized by the ionic liquid (IL) method, regardless of the heating treatment, demonstrated superior performance, with larger active areas (with furnace 82 mC cm-2, microwave 97 mC cm-2, and laser 127 mC cm-2) and higher phenol degradation rates, resulting in a greater generation of carboxylates during electrolysis, yielding primarily oxalate and achieving up to 40% conversion with furnace heating. However, laser-treated anodes exhibited greater stability than furnace-made ones, attributed to the formation of an insulating TiO2 layer. Although the electrode with the longest service life did not show the best catalytic properties for minimizing mineralization, the observed variations in coatings with identical chemical compositions highlight the importance of this research. This study positions itself at the forefront of developing more efficient and sustainable electrochemical technologies for organic waste treatment.


Assuntos
Ácidos Carboxílicos , Eletrodos , Óxidos , Óxidos/química , Ácidos Carboxílicos/química , Oxirredução , Rutênio/química , Eletrólise , Antimônio/química , Técnicas Eletroquímicas/métodos , Líquidos Iônicos/química , Catálise
20.
Prostate ; 84(14): 1336-1343, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39031050

RESUMO

BACKGROUND: There are no population-level studies assessing 18F-fluciclovine (fluciclovine) utilization of Positron emission tomography/computed tomography (PET/CT) for biochemically recurrent prostate cancer (PC). We assessed fluciclovine PET/CT in the Veterans Affairs Health Care System. METHODS: Of 1153 men with claims suggesting receipt of fluciclovine PET/CT, we randomly reviewed charts of 300 who indeed underwent fluciclovine PET/CT. The primary outcome was fluciclovine PET/CT result (positive or negative). Comparison among groups stratified by androgen deprivation therapy (ADT) (yes vs. no) and prostate-specific antigen (PSA) (≤1 vs. >1 ng/mL) at imaging were performed. Logistic regression tested associations between PSA, ADT receipt, and race with fluciclovine PET/CT positive imaging. RESULTS: Fluciclovine PET/CT positivity rate was 33% for patients with PSA 0-0.5 ng/mL, 21% for >0.5-1.0, 54% for >1.0-2.0, and 66% for >2.0 (p < 0.01). A 59% positivity rate ocurred in patients treated with concurrent ADT versus 37% in those not on ADT (p < 0.01). White were more likely to have a positive scan versus Black patients (55% vs. 38%; p = 0.02). Patients whose primary treatment was radical prostatectomy had a lower positivity rate (33%) versus those treated with radiotherapy (55%) (p < 0.001). On multivariable logistic regression, PSA > 1 ng/mL (all men odds ratio [OR]: 4.06, 95% confidence interval [CI]: 2.07-7.96; men on ADT only OR: 4.42, 95% CI: 1.73-11.26) and use of ADT (OR: 3.94, 95% CI: 1.32-11.75), and White (all men OR: 2.22, 95% CI: 1.20-4.17) predicted positive fluciclovine PET/CT. CONCLUSION: This real-world study assessing 18F-fluciclovine PET/CT performance in an equal access health care system confirms higher detection rates than traditional imaging methods, but positivity is highly influenced by PSA at time of imaging. Additionally, patients currently receiving ADT have at least four times higher likelihood of a positive scan, showing that scan positivity isn't negatively affected by ADT status in this study. Finally, White men were more likely to have a positive scan, the reasons for which should be explored in future studies.


Assuntos
Ácidos Carboxílicos , Ciclobutanos , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Ciclobutanos/uso terapêutico , Idoso , Recidiva Local de Neoplasia/diagnóstico por imagem , Pessoa de Meia-Idade , Estados Unidos , Antígeno Prostático Específico/sangue , United States Department of Veterans Affairs , Antagonistas de Androgênios/uso terapêutico
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