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Molecules (Basel, Switzerland) Dec 2022Acyl moiety is a common structural unit in organic molecules, thus acylation methods have been widely explored to construct various functional compounds. While the... (Review)
Review
Acyl moiety is a common structural unit in organic molecules, thus acylation methods have been widely explored to construct various functional compounds. While the traditional Friedel-Crafts acylation processes work to allow viable construction of arylketones under harsh acid conditions, recent progress on developing acylation methods focused on the new reactivity discovery by exploiting versatile and easily accessible acylating reagents. Of them, alcohols are cheap, have low toxicity, and are naturally abundant feedstocks; thus, they were recently used as ideal acyl precursors in molecule synthesis for ketones, esters, amides, etc. In this review, we display and discuss recent advances in employing alcohols as unusual acyl sources to form C-C and C-heteroatom bonds, with emphasis on the substrate scope, limitations, and mechanism.
Topics: Alcohols; Amides; Acylation; Ketones; Esters
PubMed: 36558110
DOI: 10.3390/molecules27248977 -
Oncotarget Feb 2017
Topics: Allosteric Site; Anesthetics; Animals; Binding Sites; DNA Mutational Analysis; Etomidate; Humans; Ions; Mutation; Neurotransmitter Agents; Oocytes; Pentobarbital; Propofol; Protein Domains; Protein Isoforms; Receptors, GABA-A; Xenopus
PubMed: 28099926
DOI: 10.18632/oncotarget.14616 -
Anesthesiology Nov 2016Etomidate potently suppresses adrenocortical steroid synthesis with potentially deleterious consequences by binding to 11β-hydroxylase and inhibiting its function. The...
BACKGROUND
Etomidate potently suppresses adrenocortical steroid synthesis with potentially deleterious consequences by binding to 11β-hydroxylase and inhibiting its function. The authors hypothesized that other sedative-hypnotics currently in clinical use or under development (or their metabolites) might bind to the same site at clinically relevant concentrations. The authors tested this hypothesis by defining etomidate's affinity for this site and the potencies with which other sedative-hypnotics (and their metabolites) inhibit etomidate binding.
METHODS
H-etomidate's binding to adrenal membranes from Sprague-Dawley rats was characterized with a filtration assay, and its dissociation constant was defined using saturation and homologous ligand competition approaches. Half-inhibitory concentrations of sedative-hypnotics and metabolites were determined from the reduction in specific H-etomidate binding measured in the presence of ranging sedative-hypnotic and metabolite concentrations.
RESULTS
Saturation and homologous competition studies yielded H-etomidate dissociation constants of 40 and 21 nM, respectively. Half-inhibitory concentrations of etomidate and cyclopropyl methoxycarbonyl metomidate (CPMM) differed significantly (26 vs. 143 nM, respectively; P < 0.001), and those of the carboxylic acid (CA) metabolites etomidate-CA and CPMM-CA were greater than or equal to 1,000× higher than their respective parent hypnotics. The half-inhibitory concentration of dexmedetomidine was 2.2 µM, whereas those of carboetomidate, ketamine, and propofol were greater than or equal to 50 µM.
CONCLUSION
Etomidate's in vitro dissociation constant for 11β-hydroxylase closely approximates its in vivo adrenocortical half-inhibitory concentration. CPMM produces less adrenocortical suppression than etomidate not only because it is metabolized faster but also because it binds to 11β-hydroxylase with lower affinity. Other sedative-hypnotics and metabolites bind to 11β-hydroxylase and inhibit etomidate binding only at suprahypnotic concentrations.
Topics: Adrenal Cortex; Anesthetics, Dissociative; Animals; Etomidate; Hypnotics and Sedatives; Ketamine; Models, Animal; Propofol; Pyrroles; Rats; Rats, Sprague-Dawley; Steroid 11-beta-Hydroxylase; Structure-Activity Relationship
PubMed: 27541316
DOI: 10.1097/ALN.0000000000001304 -
Journal of Medicine and Life Jan 2024This study aimed to identify novel Glyoxalase-I (Glo-I) inhibitors with potential anticancer properties, focusing on anthraquinone amide-based derivatives. We...
This study aimed to identify novel Glyoxalase-I (Glo-I) inhibitors with potential anticancer properties, focusing on anthraquinone amide-based derivatives. We synthesized a series of these derivatives and conducted in silico docking studies to predict their binding interactions with Glo-I. In vitro assessments were performed to evaluate the anti-Glo-I activity of the synthesized compounds. A comprehensive structure-activity relationship (SAR) analysis identified key features responsible for specific binding affinities of anthraquinone amide-based derivatives to Glo-I. Additionally, a 100 ns molecular dynamics simulation assessed the stability of the most potent compound compared to a co-crystallized ligand. Compound MQ3 demonstrated a remarkable inhibitory effect against Glo-I, with an IC concentration of 1.45 µM. The inhibitory potency of MQ3 may be attributed to the catechol ring, amide functional group, and anthraquinone moiety, collectively contributing to a strong binding affinity with Glo-I. Anthraquinone amide-based derivatives exhibit substantial potential as Glo-I inhibitors with prospective anticancer activity. The exceptional inhibitory efficacy of compound MQ3 indicates its potential as an effective anticancer agent. These findings underscore the significance of anthraquinone amide-based derivatives as a novel class of compounds for cancer therapy, supporting further research and advancements in targeting the Glo-I enzyme to combat cancer.
Topics: Humans; Amides; Anthraquinones; Antineoplastic Agents; Enzyme Inhibitors; Lactoylglutathione Lyase; Molecular Docking Simulation; Molecular Dynamics Simulation; Structure-Activity Relationship
PubMed: 38737655
DOI: 10.25122/jml-2023-0257 -
Physiological Research Apr 2023Increased incidence of postoperative cognitive dysfunction (POCD) is observed in elderly patients underwent intravenous anesthesia (TIVA) with endotracheal intubation.... (Randomized Controlled Trial)
Randomized Controlled Trial
Increased incidence of postoperative cognitive dysfunction (POCD) is observed in elderly patients underwent intravenous anesthesia (TIVA) with endotracheal intubation. Modulation of anesthetics compatibility may reduce the severity of POCD. Elderly patients scheduled for TIVA with endotracheal intubation were randomly divided into the control group (1.00?2.00 mg/kg propofol) and the etomidate and propofol combination group (1.00?2.00 mg/kg propofol and 0.30 mg/kg etomidate). Serum cortisol, S100?, and neuron-specific enolase (NSE), interleukin (IL)-6, and IL-10 were monitored during or after the operation. Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were utilized to assess the severity of POCD. 63 elderly patients in the etomidate and propofol combination group and 60 patients in the control group were enrolled, and there was no significant difference in gender, American Society of Anesthesiologists (ASA) physical status, surgical specialty, intraoperative blood loss, and operation time between the two groups. Significantly increased serum cortisol, S100?, NSE, IL-6, and reduced MMSE and MoCA scores were detected in the control group at different time points after the operation (0-72 h post operation) when compared to those before the operation. Similar trends for these observed factors were found in the etomidate and propofol combination group. In addition, the etomidate and propofol combination group showed better effects in reducing the serum levels of cortisol, S100?, NSE, IL-6, and increasing the MMSE and MoCA scores when compared to the control group. The present study demonstrates that the combination of propofol with etomidate could alleviate POCD in elderly patients underwent TIVA with endotracheal intubation anesthesia.
Topics: Aged; Humans; Postoperative Cognitive Complications; Etomidate; Propofol; Anesthesia, Intravenous; Hydrocortisone; Interleukin-6; Anesthesia, General
PubMed: 37159858
DOI: 10.33549/physiolres.934983 -
The Cochrane Database of Systematic... Mar 2015Electrical cardioversion is an effective procedure for restoring normal sinus rhythm in the hearts of patients with irregular heart rhythms. It is important that the... (Review)
Review
BACKGROUND
Electrical cardioversion is an effective procedure for restoring normal sinus rhythm in the hearts of patients with irregular heart rhythms. It is important that the patient is not fully conscious during the procedure, as it can be painful and distressing. The drug used to make patients unaware of the procedure should rapidly achieve the desired level of sedation, should wear off quickly and should not cause cardiovascular or respiratory side effects.
OBJECTIVES
We aimed to compare the safety, effectiveness and adverse events associated with various anaesthetic or sedative agents used in direct current cardioversion for cardiac arrhythmia in both elective and emergency settings.We sought answers to the following specific questions.• Which drugs deliver the best outcomes for patients undergoing electrical cardioversion?• Does using a particular agent confer advantages or disadvantages?• Is additional analgesic necessary to prevent pain?
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) on 27 March 2014. Our search terms were relevant to the review question and were not limited by outcomes. We also carried out searches of clinical trials registers and forward and backward citation tracking.
SELECTION CRITERIA
We considered all randomized controlled trials and quasi-randomized and cluster-randomized studies with adult participants undergoing electrical cardioversion procedures in the elective or emergency setting.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data, consulting with a third review author for disagreements. We used standard Cochrane methodological procedures, including assessment of risk of bias for all studies.
MAIN RESULTS
We included 23 studies with 1250 participants that compared one drug with one or more other drugs. Of these comparisons, 19 studies compared propofol with another drug. Seven of these compared propofol with etomidate (four of which combined the drugs with remifentanil or fentanyl), five midazolam, six thiopentone and two sevoflurane. Three studies compared etomidate with thiopentone, and three etomidate with midazolam. Two studies compared thiopentone with midazolam, one thiopentone with diazepam and one midazolam with diazepam. Drug doses and the time over which the drugs were given varied between studies. Although all studies were described as randomized, limited information was provided about the methods used for selection and group allocation. A high level of performance bias was observed across studies, as study authors had not attempted to blind the anaesthetist to group allocation. Similarly, study authors had rarely provided sufficient information on whether outcome assessors had been blinded.Included studies presented outcome data for hypotension, apnoea, participant recall, success of cardioversion, minor adverse events of nausea and vomiting, pain at injection site and myoclonus, additional analgesia and participant satisfaction. We did not pool the data from different studies in view of the multiple drug comparisons, differences in definitions and reporting of outcomes, variability of endpoints and high or unclear risk of bias across studies.
AUTHORS' CONCLUSIONS
Few studies reported statistically significant results for our relevant outcomes, and most study authors concluded that both, or all, agents compared in individual studies were adequate for cardioversion procedures. It is our opinion that at present, there is no evidence to suggest that current anaesthetic practice for cardioversion should change.
Topics: Anesthetics; Apnea; Diazepam; Electric Countershock; Etomidate; Fentanyl; Humans; Hypnotics and Sedatives; Hypotension; Mental Recall; Methyl Ethers; Midazolam; Piperidines; Propofol; Randomized Controlled Trials as Topic; Remifentanil; Sevoflurane; Thiopental
PubMed: 25803543
DOI: 10.1002/14651858.CD010824.pub2 -
Current Opinion in Endocrinology,... Jun 2015Primary aldosteronism is increasingly recognized as a common secondary cause of hypertension. Successful demonstration of a unilateral cause (e.g. a classical 'Conn's... (Review)
Review
PURPOSE OF REVIEW
Primary aldosteronism is increasingly recognized as a common secondary cause of hypertension. Successful demonstration of a unilateral cause (e.g. a classical 'Conn's adenoma') offers the potential for curative adrenalectomy. Adrenal vein sampling (AVS), in conjunction with cross-sectional imaging, remains the 'gold standard' for distinguishing unilateral and bilateral disease, but is technically demanding and frequently unsuccessful or inconclusive. As such, alternative strategies for lateralization, including nuclear medicine techniques, are being developed and brought into clinical practice.
RECENT FINDINGS
Metomidate, a potent ligand of CYP11B1 and CYP11B2, can be C11H3-labelled as a PET tracer and has been shown to offer a rapid noninvasive alternative to AVS for localizing unilateral aldosterone-producing adenomas.
SUMMARY
Increasing experience with 11C-metomidate PET-CT supports its use as an adjunct to AVS when this has failed, is ambiguous, or cannot be undertaken.
Topics: Etomidate; Humans; Hyperaldosteronism; Positron-Emission Tomography
PubMed: 25871964
DOI: 10.1097/MED.0000000000000148 -
The Journal of ECT Jun 2023Etomidate and methohexital are the 2 commonly used anesthetics for electroconvulsive therapy (ECT) in the United States. The objective of this study was to examine how...
OBJECTIVE
Etomidate and methohexital are the 2 commonly used anesthetics for electroconvulsive therapy (ECT) in the United States. The objective of this study was to examine how anesthetic choice between etomidate and methohexital is associated with real-world clinical outcomes.
METHODS
This naturalistic retrospective cohort study examined longitudinal electronic health records for 495 adult patients who received 2 or more ECT treatments from 2010 to 2019 in Kaiser Permanente North California, a large integrated health care system. Study outcomes included 12-month posttreatment depression remission as measured by the 9-item Patient Health Questionnaire, psychiatric and all-cause emergency department visits, and psychiatric and all-cause hospitalizations.
RESULTS
Anesthetic choice was not significantly related to depression severity, emergency department visits, or psychiatric hospitalizations at 12 months after completing ECT. In exploratory analyses, we found that etomidate compared with methohexital was associated with higher rates of patient discomfort adverse effects-postictal agitation, phlebitis, and myoclonus (2.4% vs 0.4%; P < 0.001).
CONCLUSIONS
We present the first large comparison of etomidate and methohexital as anesthetics for ECT and their associations with real-world outcomes. Our study showed no significant difference on depression remission, emergency department visits, or hospitalizations 12-months posttreatment. Thus, clinicians should focus on other patient or treatment characteristics when deciding on anesthetics for ECT. Further investigation is needed to confirm our exploratory findings that etomidate use was correlated with a higher rate of patient discomfort adverse effects relative to methohexital.
Topics: Adult; Humans; Anesthetics, Intravenous; Etomidate; Methohexital; Electroconvulsive Therapy; Propofol; Retrospective Studies
PubMed: 36729716
DOI: 10.1097/YCT.0000000000000895 -
Pediatric Endocrinology, Diabetes, and... 2022The purpose of this work was to present the current state of knowledge on the effects of frequently used therapeutic forms, selected pharmacotherapy (including... (Review)
Review
The purpose of this work was to present the current state of knowledge on the effects of frequently used therapeutic forms, selected pharmacotherapy (including glucocorticosteroids, immune checkpoint inhibitors, mitotane, metyrapone, aminoglutetimide, etomidate, ketoconazole, fluconazole), but also radiation therapy on the functioning of the hypothalamic-pituitary-adrenal axis in children and adolescent during and after oncological treatment. The most common pediatric cancers, where complications of adrenal insufficiency occur, are presented. Moreover, current recommendations how to diagnose the function of the adrenal axis in oncological pediatric patients, as well during oncological treatment as after it, including patients treated with steroids and also patients in severe stages, are reported. The rules of the treatment of adrenal dysfunction in those patients are presented. This understanding is of key importance for oncologists and endocrinologists in the process of diagnosing, treating and developing patient health care, as well as during therapy as after it, offering safety and improving the quality of life.
Topics: Adolescent; Adrenal Glands; Child; Etomidate; Fluconazole; Humans; Hypothalamo-Hypophyseal System; Immune Checkpoint Inhibitors; Ketoconazole; Metyrapone; Mitotane; Pituitary-Adrenal System; Quality of Life
PubMed: 36134674
DOI: 10.5114/pedm.2022.118319 -
Molecules (Basel, Switzerland) Sep 2022We used two-dimensional infrared spectroscopy to disentangle the broad infrared band in the amide II vibrational regions of native silk films, identifying the single...
We used two-dimensional infrared spectroscopy to disentangle the broad infrared band in the amide II vibrational regions of native silk films, identifying the single amide II modes and correlating them to specific secondary structure. Amide I and amide II modes have a strong vibrational coupling, which manifests as cross-peaks in 2D infrared spectra with frequencies determined by both the amide I and amide II frequencies of the same secondary structure. By cross referencing with well-known amide I assignments, we determined that the amide II (N-H) absorbs at around 1552 and at 1530 cm for helical and β-sheet structures, respectively. We also observed a peak at 1517 cm that could not be easily assigned to an amide II mode, and instead we tentatively assigned it to a Tyrosine sidechain. These results stand in contrast with previous findings from linear infrared spectroscopy, highlighting the ability of multidimensional spectroscopy for untangling convoluted spectra, and suggesting the need for caution when assigning silk amide II spectra.
Topics: Amides; Animals; Bombyx; Silk; Spectrophotometry, Infrared; Tyrosine; Vibration
PubMed: 36234809
DOI: 10.3390/molecules27196275