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Chemical Communications (Cambridge,... Oct 2015The γ-amino alcohol structural motif is often encountered in drugs and natural products. We developed two complementary catalytic diastereoselective methods for the...
The γ-amino alcohol structural motif is often encountered in drugs and natural products. We developed two complementary catalytic diastereoselective methods for the synthesis of N-PMP-protected γ-amino alcohols from the corresponding ketones. The anti-products were obtained through Ir-catalyzed asymmetric transfer hydrogenation, the syn-products via Rh-catalyzed asymmetric hydrogenation.
Topics: Amino Alcohols; Catalysis; Hydrogenation; Stereoisomerism
PubMed: 26273707
DOI: 10.1039/c5cc04445f -
Pacing and Clinical Electrophysiology :... May 2020
Topics: Epinephrine; Humans; Isoproterenol; Ventricular Premature Complexes
PubMed: 32115708
DOI: 10.1111/pace.13892 -
The Cochrane Database of Systematic... Jan 2016Beta-blockers are an essential part of standard therapy in adult congestive heart failure and therefore, are expected to be beneficial in children. However, congestive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Beta-blockers are an essential part of standard therapy in adult congestive heart failure and therefore, are expected to be beneficial in children. However, congestive heart failure in children differs from that in adults in terms of characteristics, aetiology, and drug clearance. Therefore, paediatric needs must be specifically investigated. This is an update of a Cochrane review previously published in 2009.
OBJECTIVES
To assess the effect of beta-adrenoceptor-blockers (beta-blockers) in children with congestive heart failure.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and LILACS up to November 2015. Bibliographies of identified studies were checked. No language restrictions were applied.
SELECTION CRITERIA
Randomised, controlled, clinical trials investigating the effect of beta-blocker therapy on paediatric congestive heart failure.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted and assessed data from the included trials.
MAIN RESULTS
We identified four new studies for the review update; the review now includes seven studies with 420 participants. Four small studies with 20 to 30 children each, and two larger studies of 80 children each, showed an improvement of congestive heart failure with beta-blocker therapy. A larger study with 161 participants showed no evidence of benefit over placebo in a composite measure of heart failure outcomes. The included studies showed no significant difference in mortality or heart transplantation rates between the beta-blocker and control groups. No significant adverse events were reported with beta-blockers, apart from one episode of complete heart block. A meta-analysis of left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) data showed a very small improvement with beta-blockers.However, there were vast differences in the age, age range, and health of the participants (aetiology and severity of heart failure; heterogeneity of diagnoses and co-morbidities); there was a range of treatments across studies (choice of beta-blocker, dosing, duration of treatment); and a lack of standardised methods and outcome measures. Therefore, the primary outcomes could not be pooled in meta-analyses.
AUTHORS' CONCLUSIONS
There is not enough evidence to support or discourage the use of beta-blockers in children with congestive heart failure, or to propose a paediatric dosing scheme. However, the sparse data available suggested that children with congestive heart failure might benefit from beta-blocker treatment. Further investigations in clearly defined populations with standardised methodology are required to establish guidelines for therapy. Pharmacokinetic investigations of beta-blockers in children are also required to provide effective dosing in future trials.
Topics: Adolescent; Adrenergic beta-Antagonists; Carbazoles; Carvedilol; Child; Child, Preschool; Heart Failure; Humans; Infant; Infant, Newborn; Metoprolol; Propanolamines; Propranolol; Randomized Controlled Trials as Topic
PubMed: 26820557
DOI: 10.1002/14651858.CD007037.pub3 -
European Journal of Medicinal Chemistry Sep 2018It is known that aziridines and nitrogen mustards exert their biological activities, especially in chemotherapy, via DNA alkylation. The studied scaffold,...
It is known that aziridines and nitrogen mustards exert their biological activities, especially in chemotherapy, via DNA alkylation. The studied scaffold, 2-phenyl-1-aziridine, provides a distinct conformation compared to commonly used aziridines, and therefore, leads to a change in high-strained ring reactivity towards biological nucleophiles, such as DNA. The above series of compounds was tested in three breast cell lines: MCF-10, a healthy cell; MCF-7, a hormone responsive cancer cell; and MDA-MB-231, a triple negative breast cancer cell. Both aziridines and their precursors, β-amino alcohols, showed activity towards these cells, and some of the compounds showed higher selectivity index than cisplatin, the drug used as control. When the type of cell death was investigated, the synthesized compounds demonstrated higher apoptosis and lower necrosis rates than cisplatin, and when the mechanism of action was studied, the compounds were shown to interact with DNA via its minor groove instead of alkylation or intercalation.
Topics: Alkylation; Amino Alcohols; Antineoplastic Agents; Aziridines; Cell Line; Cisplatin; DNA; Dose-Response Relationship, Drug; Humans; Molecular Structure; Structure-Activity Relationship
PubMed: 30125724
DOI: 10.1016/j.ejmech.2018.07.055 -
Journal of Biomolecular Structure &... Oct 2022Fungi are being responsible for causing serious infections in humans and animals. The opportunistic microorganisms provoke environmental contaminations in health and...
Antifungal activity of amino-alcohols based cationic surfactants and in silico, homology modeling, docking and molecular dynamics studies against lanosterol 14-α-demethylase enzyme.
Fungi are being responsible for causing serious infections in humans and animals. The opportunistic microorganisms provoke environmental contaminations in health and storage facilities to represent a serious concern to health security. The present work investigates the antifungal activity of two amino-alcohols based cationic surfactants such as CEtOH, CPrOH (with = 14 and 16 are the carbon numbers of alkyl chain and EtOH = Ethanol and PrOH = Propanol) against a collection of different species (, , respectively. The amino-alcohols based cationic surfactants exhibited good antifungal activity against all strains tested with minimum inhibitory concentrations (MIC) ranging from 0.002 to 0.30 mM. The MIC evaluation shows an increase as a function of the hydrophobicity of all inhibitors against the majority of the strains tested. The different location of the alcoholic OH function in the polar head shows the influence on the availability of N responsible for electrostatic interactions with the candidate's cell walls, which remains a very important step in the mode of action of quaternary ammonium cationic surfactants. Hence, a 3D structure of lanosterol 14-α-demethylase enzyme from was constructed by homology modeling using an online SWISS-MODEL server. The predicted model was analyzed by serval servers. Furthermore, a molecular docking study was carried out to better understand the binding mechanism of lanosterol homologous protein with surfactant ligands. Then, the docked complexes lanosterol-surfactants were refined by the molecular dynamic simulation to analyze their interaction behavior during the simulation.Communicated by Ramaswamy H. Sarma.
Topics: Amino Alcohols; Ammonium Compounds; Animals; Antifungal Agents; Candida; Candida albicans; Carbon; Ethanol; Humans; Lanosterol; Microbial Sensitivity Tests; Molecular Docking Simulation; Molecular Dynamics Simulation; Propanols; Sterol 14-Demethylase; Surface-Active Agents
PubMed: 33754947
DOI: 10.1080/07391102.2021.1902396 -
Angewandte Chemie (International Ed. in... Jul 2020Capture and release of peptides is often a critical operation in the pathway to discovering materials with novel functions. However, the best methods for efficient...
Capture and release of peptides is often a critical operation in the pathway to discovering materials with novel functions. However, the best methods for efficient capture impede facile release. To overcome this challenge, we report linkers based on secondary amino alcohols for the release of peptides after capture. These amino alcohols are based on serine (seramox) or isoserine (isoseramox) and can be incorporated into peptides during solid-phase peptide synthesis through reductive amination. Both linkers are quantitatively cleaved within minutes under NaIO treatment. Cleavage of isoseramox produced a native peptide N-terminus. This linker also showed broad substrate compatibility; incorporation into a synthetic peptide library resulted in the identification of all sequences by nanoLC-MS/MS. The linkers are cell compatible; a cell-penetrating peptide that contained this linker was efficiently captured and identified after uptake into cells. These findings suggest that such secondary amino alcohol based linkers might be suitable tools for peptide-discovery platforms.
Topics: Amino Alcohols; Peptide Library; Peptides; Protein Conformation
PubMed: 32227406
DOI: 10.1002/anie.202003478 -
Organic Letters Dec 2020We report a DNA-compatible photoredox decarboxylative coupling of α-amino acids with carbonyl compounds to access DNA-encoded sp-rich 1,2-amino alcohols. The reaction...
We report a DNA-compatible photoredox decarboxylative coupling of α-amino acids with carbonyl compounds to access DNA-encoded sp-rich 1,2-amino alcohols. The reaction proceeds efficiently for a wide range of DNA-conjugated aldehydes and ketones and provides the desired 1,2-amino alcohols with conversions generally >50%. Additional utility of the developed protocol is demonstrated by one-pot cyclization of DNA-conjugated 1,2-amino alcohols into oxazolidiones and morpholinones. Lastly, qPCR and sequencing data analysis indicates no significant DNA damage upon photoredox decarboxylative coupling.
Topics: Amino Alcohols; Catalysis; Cyclization; DNA; Ketones; Molecular Structure; Oxidation-Reduction
PubMed: 33170713
DOI: 10.1021/acs.orglett.0c03461 -
Cancer Research Oct 2021Catecholamines, which are involved in response to physical or emotional stress, have emerged as one of the main mediators of the relationship between chronic stress and...
Catecholamines, which are involved in response to physical or emotional stress, have emerged as one of the main mediators of the relationship between chronic stress and cancer progression. The study in this issue of by Liu and colleagues reveals a new mechanism by which psychologic stress stimulates cancer progression through the D2 dopamine receptor and activation of the oxygen-independent HIF1α pathway. Although most investigations so far have focused on the action of the stress-related catecholamines norepinephrine and epinephrine on tumor cells, this study shows that dopamine and its receptor can be a potential therapeutic target. The findings broaden the understanding of the interaction of catecholamines with the tumor microenvironment and reinforces the need to look at psychologic stress as a modulator of cancer progression..
Topics: Catecholamines; Dopamine; Epinephrine; Neoplasms; Norepinephrine; Stress, Psychological
PubMed: 34654699
DOI: 10.1158/0008-5472.CAN-21-3077 -
Chembiochem : a European Journal of... Jan 2021Optically active β-amino alcohols are very useful chiral intermediates frequently used in the preparation of pharmaceutically active substances. Here, a novel...
Enantioselective Cascade Biocatalysis for Deracemization of Racemic β-Amino Alcohols to Enantiopure (S)-β-Amino Alcohols by Employing Cyclohexylamine Oxidase and ω-Transaminase.
Optically active β-amino alcohols are very useful chiral intermediates frequently used in the preparation of pharmaceutically active substances. Here, a novel cyclohexylamine oxidase (ArCHAO) was identified from the genome sequence of Arthrobacter sp. TYUT010-15 with the R-stereoselective deamination activity of β-amino alcohol. ArCHAO was cloned and successfully expressed in E. coli BL21, purified and characterized. Substrate-specific analysis revealed that ArCHAO has high activity (4.15 to 6.34 U mg protein) and excellent enantioselectivity toward the tested β-amino alcohols. By using purified ArCHAO, a wide range of racemic β-amino alcohols were resolved, (S)-β-amino alcohols were obtained in >99 % ee. Deracemization of racemic β-amino alcohols was conducted by ArCHAO-catalyzed enantioselective deamination and transaminase-catalyzed enantioselective amination to afford (S)-β-amino alcohols in excellent conversion (78-94 %) and enantiomeric excess (>99 %). Preparative-scale deracemization was carried out with 50 mM (6.859 g L ) racemic 2-amino-2-phenylethanol, (S)-2-amino-2-phenylethanol was obtained in 75 % isolated yield and >99 % ee.
Topics: Amino Alcohols; Arthrobacter; Biocatalysis; Molecular Structure; Oxidoreductases Acting on CH-NH Group Donors; Stereoisomerism; Transaminases
PubMed: 32789939
DOI: 10.1002/cbic.202000491 -
British Journal of Pharmacology Nov 2018The calcium-sensing receptor (CaS receptor) plays a pivotal role in extracellular calcium homeostasis, and germline loss-of-function and gain-of-function mutations cause... (Review)
Review
UNLABELLED
The calcium-sensing receptor (CaS receptor) plays a pivotal role in extracellular calcium homeostasis, and germline loss-of-function and gain-of-function mutations cause familial hypocalciuric hypercalcaemia (FHH) and autosomal dominant hypocalcaemia (ADH), respectively. CaS receptor signal transduction in the parathyroid glands is probably regulated by G-protein subunit α (Gα ) and adaptor-related protein complex-2 σ-subunit (AP2σ), and recent studies have identified germline mutations of these proteins as a cause of FHH and/or ADH. Calcimimetics and calcilytics are positive and negative allosteric modulators of the CaS receptor that have potential efficacy for symptomatic forms of FHH and ADH. Cellular studies have demonstrated that these compounds correct signalling and/or trafficking defects caused by mutant CaS receptor, Gα or AP2σ proteins. Moreover, mouse model studies indicate that calcilytics can rectify the hypocalcaemia and hypercalciuria associated with ADH, and patient-based studies reveal calcimimetics to ameliorate symptomatic hypercalcaemia caused by FHH. Thus, calcimimetics and calcilytics represent targeted therapies for inherited disorders of the CaS receptor signalling pathway.
LINKED ARTICLES
This article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.21/issuetoc.
Topics: Allosteric Regulation; Amino Alcohols; Animals; Calcimimetic Agents; Humans; Receptors, Calcium-Sensing; Signal Transduction
PubMed: 29127708
DOI: 10.1111/bph.14086