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Journal of Hazardous Materials Feb 2023The recalcitrant β-blockers have been widely detected in aquatic environments up to several hundred μg/L, which are major contributors to β1 antagonistic activities...
The recalcitrant β-blockers have been widely detected in aquatic environments up to several hundred μg/L, which are major contributors to β1 antagonistic activities in wastewater. Their biodegradation mechanisms remain obscure, hindering the development of efficient removal techniques. This study constructed the biodegradation pathways for three typical β-blockers, namely atenolol, metoprolol, and propranolol, assessed the toxicity of their major biotransformation products, and identified the key enzyme catalyzing the O-dealkylation reaction leading to pollutant mineralization. Atenolol and metoprolol degradation was more efficient than that of propranolol by activated sludge, producing metoprolol acid (MTPA) as a major intermediate. Hydrogenophaga sp. YM1 isolated from activated sludge possess the α-ketoglutarate dependent dioxygenase (TfdA) responsible for O-dealkylation of MTPA and propranolol, producing 4-hydroxyphenylacetic acid (4-HPA) that can be further degraded and ultimately enters the TCA cycle. The role of TfdA was verified by proteomics, enzyme stimulation/inhibition tests, and gene knockout experiments. Molecular docking suggests its different interactions with MTPA and propranolol. Acetate facilitated the degradation of β-blockers efficiently. The results may shed light on enhanced biological removals of broader β-blockers and their transformation products in the environment.
Topics: Wastewater; Propranolol; Metoprolol; Sewage; Atenolol; Molecular Docking Simulation; Adrenergic beta-Antagonists
PubMed: 36417780
DOI: 10.1016/j.jhazmat.2022.130338 -
Methods in Molecular Biology (Clifton,... 2023Fatty acid amide hydrolase (FAAH) is an intracellular enzyme responsible for the hydrolysis of endogenous anandamide (AEA), a reaction that terminates the biological...
Fatty acid amide hydrolase (FAAH) is an intracellular enzyme responsible for the hydrolysis of endogenous anandamide (AEA), a reaction that terminates the biological effects of this lipid mediator. The final products of AEA cleavage are arachidonic acid and ethanolamine. In the method described herein, FAAH activity is measured through the use of the radioactive substrate [C-ethanolamine]-AEA and subsequent quantification of the reaction product [C]-ethanolamine.
Topics: Amidohydrolases; Arachidonic Acid; Brain; Endocannabinoids; Ethanolamine; Ethanolamines; Hydrolysis
PubMed: 36152192
DOI: 10.1007/978-1-0716-2728-0_20 -
Tumour Biology : the Journal of the... Apr 2017Elucidating the interaction between cancer and non-cancer cells, such as blood vessels, immune cells, and other stromal cells, in the tumor microenvironment is... (Review)
Review
Elucidating the interaction between cancer and non-cancer cells, such as blood vessels, immune cells, and other stromal cells, in the tumor microenvironment is imperative in understanding the mechanisms underlying cancer progression and metastasis, which is expected to lead to the development of new therapeutics. Sphingosine-1-phosphate is a bioactive lipid mediator that promotes cell survival, proliferation, migration, angiogenesis/lymphangiogenesis, and immune responsiveness, which are all factors involved in cancer progression. Sphingosine-1-phosphate is generated inside cancer cells by sphingosine kinases and then exported into the tumor microenvironment. Although sphingosine-1-phosphate is anticipated to play an important role in the tumor microenvironment and cancer progression, determining sphingosine-1-phosphate levels in the tumor microenvironment has been difficult due to a lack of established methods. We have recently developed a method to measure sphingosine-1-phosphate levels in the interstitial fluid that bathes cancer cells in the tumor microenvironment, and reported that high levels of sphingosine-1-phosphate exist in the tumor interstitial fluid. Importantly, sphingosine-1-phosphate can be secreted from cancer cells and non-cancer components such as immune cells and vascular/lymphatic endothelial cells in the tumor microenvironment. Furthermore, sphingosine-1-phosphate affects both cancer and non-cancer cells in the tumor microenvironment promoting cancer progression. Here, we review the roles of sphingosine-1-phosphate in the interaction between cancer and non-cancer cells in tumor microenvironment, and discuss future possibilities for targeted therapies against sphingosine-1-phosphate signaling for cancer patients.
Topics: Humans; Lysophospholipids; Neoplasms; Sphingosine; Tumor Microenvironment
PubMed: 28381169
DOI: 10.1177/1010428317699133 -
Angewandte Chemie (International Ed. in... Apr 2022The chiral N-substituted 1,2-amino alcohol motif is found in many natural and synthetic bioactive compounds. In this study, enzymatic asymmetric reductive amination of...
Asymmetric Synthesis of N-Substituted 1,2-Amino Alcohols from Simple Aldehydes and Amines by One-Pot Sequential Enzymatic Hydroxymethylation and Asymmetric Reductive Amination.
The chiral N-substituted 1,2-amino alcohol motif is found in many natural and synthetic bioactive compounds. In this study, enzymatic asymmetric reductive amination of α-hydroxymethyl ketones with enantiocomplementary imine reductases (IREDs) enabled the synthesis of chiral N-substituted 1,2-amino alcohols with excellent ee values (91-99 %) in moderate to high yields (41-84 %). Furthermore, a one-pot, two-step enzymatic process involving benzaldehyde lyase-catalyzed hydroxymethylation of aldehydes and subsequent asymmetric reductive amination was developed, offering an environmentally friendly and economical way to produce N-substituted 1,2-amino alcohols from readily available simple aldehydes and amines. This methodology was then applied to rapidly access a key synthetic intermediate of anti-malaria and cytotoxic tetrahydroquinoline alkaloids.
Topics: Aldehydes; Amination; Amines; Amino Alcohols; Stereoisomerism
PubMed: 35166000
DOI: 10.1002/anie.202116344 -
Journal of Biotechnology Jan 2019Chiral β-amino alcohols are very important chiral building block for preparing bioactive compounds for use in pharmaceutical and fine chemical industries. Synthesis of...
Enantioselective synthesis of enantiopure β-amino alcohols via kinetic resolution and asymmetric reductive amination by a robust transaminase from Mycobacterium vanbaalenii.
Chiral β-amino alcohols are very important chiral building block for preparing bioactive compounds for use in pharmaceutical and fine chemical industries. Synthesis of chiral β-amino alcohols by transaminase is big challenging due to the strict substrate specificities and very low activity of the enzyme. In this work, a (R)-selective ω-transaminase (MVTA) from Mycobacterium vanbaalenii was employed as a biocatalyst for the first time for the synthesis of chiral β-amino alcohol via kinetic resolution and asymmetric reductive amination. The enzyme was purified and characterized. Kinetic resolution of a set of racemic β-amino alcohols including two cyclic β-amino alcohols by MVTA was demonstrated, affording (R)-β-amino alcohols, (1S, 2S)-trans-2-aminocyclopentanol and (1R, 2S)-cis-1-amino-2-indanols in >99% ee and 50-62% conversion. Asymmetric reductive amination of three α-hydroxy ketones (10-300 mM) by MVTA was conducted, (S)-β-amino alcohols were obtained with >99% ee and 80-99% conversion. Preparation experiment for the reductive amination of 200 mM 2-hydroxyacetophenone by the resting cells of recombinant E. coli (MVTA) was proceeded smoothly and product (S)-2-amino-2-phenylethanol was obtained with 71% isolated yield, >99% ee and 68.6 g/L/d volumetric productivity. The current research proved that the MVTA is a robust enzyme for the preparation of chiral β-amino alcohol with high volumetric productivity.
Topics: Amino Alcohols; Bacterial Proteins; Bioreactors; Escherichia coli; Kinetics; Mycobacterium; Recombinant Proteins; Stereoisomerism; Transaminases
PubMed: 30553805
DOI: 10.1016/j.jbiotec.2018.12.003 -
Langmuir : the ACS Journal of Surfaces... Jul 2023Prebiotic membranes are one of the essential elements of the origin of life because they build compartments to keep genetic materials and metabolic machinery safe. Since...
Prebiotic membranes are one of the essential elements of the origin of life because they build compartments to keep genetic materials and metabolic machinery safe. Since modern cell membranes are made up of ethanolamine-based phospholipids, prebiotic membrane formation with ethanolamine-based amphiphiles and phosphates might act as a bridge between the prebiotic and contemporary eras. Here, we report the prebiotic synthesis of -lauroyl ethanolamine (OLEA), -lauroyl methyl ethanolamine (OLMEA), and -lauroyl dimethylethanolamine (OLDMEA) under wet-dry cycles. Turbidimetric, NMR, DLS, fluorescence, microscopy, and glucose encapsulation studies highlighted that OLEA-ATP and OLMEA-ATP form protocellular membranes in a 3:1 ratio, where ATP acts as a template. OLDMEA with a dimethyl group did not form any membrane in the presence of ATP. ADP can also template OLEA to form vesicles in a 2:1 ratio, but the ADP-templated vesicles were smaller. This suggests the critical role of the phosphate backbone in controlling the curvature of supramolecular assembly. The mechanisms of hierarchical assembly and transient dissipative assembly are discussed based on templated-complex formation via electrostatic, hydrophobic, and H-bonding interactions. Our results suggest that methylethanolamine-based amphiphiles could be used to form prebiotic vesicles, but the superior H-bonding ability of the ethanolamine moiety likely provides an evolutionary advantage for stable protocell formation during the fluctuating environments of early earth.
Topics: Ethanolamine; Ethanolamines; Membranes; Cell Membrane; Phospholipids; Phosphates
PubMed: 37421360
DOI: 10.1021/acs.langmuir.3c00600 -
Acta Tropica Jun 2018Cystic echinococcosis is a globally distributed zoonotic disease, which is caused by the larval stage of Echinococcosus granulosus sensu lato. The chemotherapy of the...
Cystic echinococcosis is a globally distributed zoonotic disease, which is caused by the larval stage of Echinococcosus granulosus sensu lato. The chemotherapy of the disease is limited to the use of benzimidazoles. Recently, mefloquine and its analogues, aminoalcohol-carbazole, and some amino alcohol derivatives were reported to display inhibitory effects on parasites. Here, the activities of 130 amino alcohol compounds against E. granulosus were tested on protoscoleces and germinal cells at a concentration of 20 μg/ml over a period of three days. As a result, sixteen compounds totally were effective against both protoscoleces and germinal cells, and their IC and LC were also calculated respectively. Then effects of the most active compounds were observed on metacestodes over 14 days in vitro. Although the structure of active compounds were variable, hydroxyl and amino groups connected by two carbon atoms are held in common as the key feature of these compounds. The further investigation on metacestodes incubated with these active compounds revealed that the effects of JF16 and BTB4 were comparable to that of mefloquine and mebendazole. In addition, the ultrastructure alternations induced by these compounds on E. granulosus were confirmed by scanning electron microscopy and transmission electron microscopy observations. In conclusion, amino alcohols were a class of compounds with efficacy against E. granulosus. The most effective compounds JF16 and BTB4 indicated that their basic structure would be useful in the synthesis of new compound for the treatment of echinococcosis. However, their in vivo efficacy and toxicity need to be carefully evaluated in the future.
Topics: Amino Alcohols; Animals; Antiparasitic Agents; Echinococcosis; Echinococcus granulosus; Mebendazole; Mefloquine; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission
PubMed: 28859963
DOI: 10.1016/j.actatropica.2017.08.031 -
Phytotherapy Research : PTR Aug 2020Confusion and misunderstanding exist regarding the lack of cardiovascular and other adverse health effects of p-synephrine and p-octopamine relative to ephedrine and... (Review)
Review
Confusion and misunderstanding exist regarding the lack of cardiovascular and other adverse health effects of p-synephrine and p-octopamine relative to ephedrine and m-synephrine (phenylephrine) which are known for their effects on the cardiovascular system. These four molecules have some structural similarities. However, the structural and stereochemical differences of p-synephrine and p-octopamine as related to ephedrine and m-synephrine result in markedly different adrenergic receptor binding characteristics as well as other mechanistic differences which are reviewed. p-Synephrine and p-octopamine exhibit little binding to α-1, α-2, β-1 and β-2 adrenergic receptors, nor are they known to exhibit indirect actions leading to an increase in available levels of endogenous norepinephrine and epinephrine at commonly used doses. The relative absence of these mechanistic actions provides an explanation for their lack of production of cardiovascular effects at commonly used oral doses as compared to ephedrine and m-synephrine. As a consequence, the effects of ephedrine and m-synephrine cannot be directly extrapolated to p-synephrine and p-octopamine which exhibit significantly different pharmacokinetic, and physiological/pharmacological properties. These conclusions are supported by human, animal and in vitro studies that are discussed.
Topics: Animals; Ephedrine; Humans; Octopamine; Rats; Synephrine
PubMed: 32101364
DOI: 10.1002/ptr.6649 -
Chemistry (Weinheim An Der Bergstrasse,... Nov 2022A sterically encumbered aminoborane sensor is introduced and used for quantitative stereochemical analysis of monoalcohols, diols and amino alcohols. The small-molecule...
A sterically encumbered aminoborane sensor is introduced and used for quantitative stereochemical analysis of monoalcohols, diols and amino alcohols. The small-molecule probe exhibits a rigid ortho-substituted arene scaffold with a proximate boron binding site and a triarylamine circular dichroism (CD) reporter unit which proved to be crucial for the observed chiroptical signal induction. Coordination of the chiral target molecule produces strong Cotton effects and UV changes that are readily correlated to its absolute configuration, enantiomeric composition and concentration to achieve comprehensive stereochemical analysis within a 5 % absolute error margin. The sensing method was successfully applied in the chromatography-free analysis of less than one milligram of a crude asymmetric reaction mixture and the advantages of this chiroptical sensing approach, which is amenable to high-throughput experimentation equipment and automation, over traditional methods is discussed.
Topics: Stereoisomerism; Amino Alcohols; Circular Dichroism; Indicators and Reagents; Boron
PubMed: 35796635
DOI: 10.1002/chem.202202028 -
Biomedical Chromatography : BMC Dec 2020A micellar liquid chromatographic method was developed for the green enantioseparation of racemic amino alcohols using an aqueous solution of the mixed surfactants as an...
A micellar liquid chromatographic method was developed for the green enantioseparation of racemic amino alcohols using an aqueous solution of the mixed surfactants as an alternative for organic solvents. In this study, the derivatives of the amino alcohols were synthesized using highly reactive chiral esters of (S)-levofloxacin (Lfx) under microwave conditions, and an aqueous solution of the surfactants (Brij-35 and SDS) was used for the enantioseparation of the synthesized diastereomeric derivatives (DDs) of amino alcohols using reversed-phase HPLC. The activated ester of Lfx was synthesized by reacting with N-hydroxybenzotriazole and characterized using UV, IR, H NMR, high-resolution mass spectrometry, and elemental analysis. The DDs of racemic amino alcohols were separated on a C column using micellar LC. Chromatographic conditions were optimized by varying the concentration of the surfactants in aqueous solution and by varying the concentration and pH of the buffer. The green assessment score was calculated for the developed method (score: 82, an excellent green method). In addition, the density functional theory calculations were performed to develop the lowest energy-optimized structures of DDs. The method was validated according to the International Conference of Harmonization guidelines, and the retention factor (k), selectivity factor (α), resolution factor (R ), limit of detection (0.198 ng mL or 0.291 pM mL ), and limit of quantification (0.594 ng mL or 0.873 pM mL ) were calculated.
Topics: Amino Alcohols; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Green Chemistry Technology; Levofloxacin; Limit of Detection; Linear Models; Micelles; Reproducibility of Results; Stereoisomerism
PubMed: 32706423
DOI: 10.1002/bmc.4954