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Medicina (Kaunas, Lithuania) Jun 2022There is a growing interest regarding the impact of the perioperative period and the application of anesthetic drugs on the recurrence of cancer metastases. Among them,... (Review)
Review
There is a growing interest regarding the impact of the perioperative period and the application of anesthetic drugs on the recurrence of cancer metastases. Among them, the use of amide-type local anesthetics seems promising since in vitro studies and animal models have shown their potential to inhibit the Intercellular Adhesion Molecule 1 (ICAM-1) expression and Src activity, which are clearly implicated in the process of inflammation and cancer metastases. This review emphasizes the potential of amide-type local anesthetics in this context.
Topics: Amides; Anesthetics, Local; Animals; Inflammation; Neoplasms
PubMed: 35888601
DOI: 10.3390/medicina58070882 -
Frontiers in Cellular and Infection... 2023Mycobacteria assemble a complex cell wall with cross-linked peptidoglycan (PG) which plays an essential role in maintenance of cell wall integrity and tolerance to...
INTRODUCTION
Mycobacteria assemble a complex cell wall with cross-linked peptidoglycan (PG) which plays an essential role in maintenance of cell wall integrity and tolerance to osmotic pressure. We previously demonstrated that various hydrolytic enzymes are required to remodel PG during essential processes such as cell elongation and septal hydrolysis. Here, we explore the chemistry associated with PG cross-linking, specifically the requirement for amidation of the D-glutamate residue found in PG precursors.
METHODS
Synthetic fluorescent probes were used to assess PG remodelling dynamics in live bacteria. Fluorescence microscopy was used to assess protein localization in live bacteria and CRISPR-interference was used to construct targeted gene knockdown strains. Time-lapse microscopy was used to assess bacterial growth. Western blotting was used to assess protein phosphorylation.
RESULTS AND DISCUSSION
In , we confirmed the essentiality for D-glutamate amidation in PG biosynthesis by labelling cells with synthetic fluorescent PG probes carrying amidation modifications. We also used CRISPRi targeted knockdown of genes encoding the MurT-GatD complex, previously implicated in D-glutamate amidation, and demonstrated that these genes are essential for mycobacterial growth. We show that MurT-rseGFP co-localizes with mRFP-GatD at the cell poles and septum, which are the sites of cell wall synthesis in mycobacteria. Furthermore, time-lapse microscopic analysis of MurT-rseGFP localization, in fluorescent D-amino acid (FDAA)-labelled mycobacterial cells during growth, demonstrated co-localization with maturing PG, suggestive of a role for PG amidation during PG remodelling and repair. Depletion of MurT and GatD caused reduced PG cross-linking and increased sensitivity to lysozyme and β-lactam antibiotics. Cell growth inhibition was found to be the result of a shutdown of PG biosynthesis mediated by the serine/threonine protein kinase B (PknB) which senses uncross-linked PG. Collectively, these data demonstrate the essentiality of D-glutamate amidation in mycobacterial PG precursors and highlight the MurT-GatD complex as a novel drug target.
Topics: Amides; Glutamic Acid; Mycobacterium smegmatis; Cell Wall; Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor; Bacterial Proteins; Peptidoglycan
PubMed: 37692163
DOI: 10.3389/fcimb.2023.1205829 -
Molecules (Basel, Switzerland) Jan 2024This review covers the last 25 years of the literature on analogs of suberoylanilide hydroxamic acid (SAHA, known also as vorinostat) acting as an HDAC inhibitor. In... (Review)
Review
This review covers the last 25 years of the literature on analogs of suberoylanilide hydroxamic acid (SAHA, known also as vorinostat) acting as an HDAC inhibitor. In particular, the topic has been focused on the synthesis and biological activity of compounds where the phenyl group (the surface recognition moiety, CAP) of SAHA has been replaced by an azaheterocycle through a direct bond with amide nitrogen atom, and the methylene chain in the linker region is of variable length. Most of the compounds displayed good to excellent inhibitory activity against HDACs and in many cases showed antiproliferative activity against human cancer cell lines.
Topics: Humans; Vorinostat; Histone Deacetylases; Amides; Histone Deacetylase Inhibitors; Cell Line
PubMed: 38202821
DOI: 10.3390/molecules29010238 -
Anesthesiology Nov 2014
Topics: Anesthetics, Intravenous; Cardiac Surgical Procedures; Etomidate; Female; Humans; Male; Postoperative Complications
PubMed: 25335176
DOI: 10.1097/ALN.0000000000000418 -
Magnetic Resonance in Medicine Jan 2023Chemical exchange saturation transfer (CEST) MRI is promising for detecting dilute metabolites and microenvironment properties, which has been increasingly adopted in...
PURPOSE
Chemical exchange saturation transfer (CEST) MRI is promising for detecting dilute metabolites and microenvironment properties, which has been increasingly adopted in imaging disorders such as acute stroke and cancer. However, in vivo CEST MRI quantification remains challenging because routine asymmetry analysis (MTR ) or Lorentzian decoupling measures a combined effect of the labile proton concentration and its exchange rate. Therefore, our study aimed to quantify amide proton concentration and exchange rate independently in a cardiac arrest-induced global ischemia rat model.
METHODS
The amide proton CEST (APT) effect was decoupled from tissue water, macromolecular magnetization transfer, nuclear Overhauser enhancement, guanidinium, and amine protons using the image downsampling expedited adaptive least-squares (IDEAL) fitting algorithm on Z-spectra obtained under multiple RF saturation power levels, before and after global ischemia. Omega plot analysis was applied to determine amide proton concentration and exchange rate simultaneously.
RESULTS
Global ischemia induces a significant APT signal drop from intact tissue. Using the modified omega plot analysis, we found that the amide proton exchange rate decreased from 29.6 ± 5.6 to 12.1 ± 1.3 s (P < 0.001), whereas the amide proton concentration showed little change (0.241 ± 0.035% vs. 0.202 ± 0.034%, P = 0.074) following global ischemia.
CONCLUSION
Our study determined the labile proton concentration and exchange rate underlying the in vivo APT MRI. The significant change in the exchange rate, but not the concentration of amide proton demonstrated that the pH effect dominates the APT contrast during tissue ischemia.
Topics: Animals; Rats; Protons; Magnetic Resonance Imaging; Hydrogen-Ion Concentration; Amides; Ischemia
PubMed: 36089834
DOI: 10.1002/mrm.29444 -
Chemistry (Weinheim An Der Bergstrasse,... Sep 2022The ubiquity of amide bonds, present in natural products and common pharmaceuticals renders this functional group one of the most prevalent in organic chemistry. Despite...
The ubiquity of amide bonds, present in natural products and common pharmaceuticals renders this functional group one of the most prevalent in organic chemistry. Despite its importance and a wide variety of existing methods for its formation, the latter still can be a challenge for classical activating reagents such as chloridating agents or carbodiimides. As the spent reagents often cannot be recycled, the development of more sustainable methods is highly desirable. Herein, we report an operationally simple and mild indirect electrochemical protocol to effect the condensation of carboxylic acids with amines, forming a wide variety of carboxamides.
Topics: Amides; Amines; Biological Products; Carbodiimides; Carboxylic Acids; Indicators and Reagents; Iodides; Pharmaceutical Preparations
PubMed: 35835720
DOI: 10.1002/chem.202201768 -
Drug Design, Development and Therapy 2017To investigate the effect of dexmedetomidine in the prevention of etomidate-induced myoclonus. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To investigate the effect of dexmedetomidine in the prevention of etomidate-induced myoclonus.
METHODS
We searched for randomized controlled trials (RCTs) regarding the use of dexmedetomidine in preventing etomidate-induced myoclonus in the databases PubMed, EMBASE, the Cochrane Library, and CNKI. We extracted data and assessed the quality of the literature and adopted RevMan 5.2 to conduct meta-analysis on each effective index and employed funnel plot to test publication bias.
RESULTS
The results showed that the incidence of etomidate-induced myoclonus in the dexmedetomidine treated groups was significantly lower than that of the control groups (risk ratio [RR]=0.27, 95% confidence interval [CI] [0.15, 0.47], <0.00001). With regard to the severity of etomidate-induced myoclonus, incidences of etomidate-induced myoclonus in the dexmedetomidine treated groups resulting in mild myoclonus (RR=0.37, 95% CI [0.19, 0.75], =0.006), moderate myoclonus (RR=0.21, 95% CI [0.12, 0.37], <0.00001), or severe myoclonus (RR=0.18, 95% CI [0.08, 0.38], <0.00001) were significantly lower than those of the control groups. No statistically significant difference was found (RR=0.70, 95% CI [0.47, 1.04], =0.08) between etomidate-induced myoclonus in the dexmedetomidine treated groups and that of the midazolam treated groups.
CONCLUSION
Dexmedetomidine can effectively prevent the incidence of etomidate-induced myoclonus and reduce the severity of etomidate-induced myoclonus. In addition, there were no significant differences between the effects of dexmedetomidine and midazolam in preventing etomidate-induced myoclonus.
Topics: Dexmedetomidine; Etomidate; Humans; Hypnotics and Sedatives; Myoclonus
PubMed: 28223779
DOI: 10.2147/DDDT.S121979 -
Molecules (Basel, Switzerland) Jul 2019A series of disubstituted 1-pyrazoles with methyl (), amino (), and nitro () groups, as well as ester () or amide () groups in positions 3 and 5 was synthesized, and...
A series of disubstituted 1-pyrazoles with methyl (), amino (), and nitro () groups, as well as ester () or amide () groups in positions 3 and 5 was synthesized, and annular tautomerism was investigated using X-ray, theoretical calculations, NMR, and FT-IR methods. The X-ray experiment in the crystal state showed for the compounds with methyl (, ) and amino () groups the tautomer with ester or amide groups at position 3 (tautomer 3), but for those with a nitro group (, ), tautomer 5. Similar results were obtained in solution by NMR NOE experiments in CDCl, DMSO-, and CDOD solvents. However, tautomer equilibrium was observed for in DMSO. The FT-IR spectra in chloroform and acetonitrile showed equilibria, which can be ascribed to conformational changes of the cis/trans arrangement of the ester/amide group and pyrazole ring. Theoretical analysis using the M06-2X/6-311++G(d,p) method (in vacuo, chloroform, acetonitrile, and water) and measurement of aromaticity (NICS) showed dependence on internal hydrogen bonds, the influence of the environment, and the effect of the substituent. These factors, pyrazole aromaticity and intra- and inter-molecular interactions, seem to have a considerable influence on the choice of tautomer.
Topics: Amides; Crystallography, X-Ray; Esters; Hydrogen Bonding; Models, Molecular; Models, Theoretical; Molecular Conformation; Molecular Structure; Pyrazoles; Spectrum Analysis
PubMed: 31330976
DOI: 10.3390/molecules24142632 -
PeerJ 2022ET-26 hydrochloride (ET-26HCl) is a novel analogue of etomidate approved for clinical trials. However, all results from recent studies were accomplished in young adult...
BACKGROUND
ET-26 hydrochloride (ET-26HCl) is a novel analogue of etomidate approved for clinical trials. However, all results from recent studies were accomplished in young adult animals. The objective of this study was to evaluate the efficacy and safety of ET-26HCl in aged rats.
METHODS
Aged Sprague-Dawley rats were randomly divided into three groups (three males and three females in each group) were given dose of two-fold of median effective dose (ED) of ET-26HCl, etomidate and propofol: the measurements of loss of the righting reflex (LORR) and cardiovascular and respiratory function after injection at the two-fold dose of the median effective dose were used for evaluation of effectiveness and safety, and the modified adrenocorticotropic hormone-stimulation experiment was used to evaluate the inhibition effect of the drugs on the synthesis of adrenal cortical hormones.
RESULTS
There was no significant difference in the onset time among propofol, etomidate and ET-26HCl. The duration of propofol (850.5 ± 77.4 s) was significantly longer than that caused by etomidate (489.8 ± 77.0 s, = 0.007) and ET-26HCl (347.3 ± 49.0 s, = 0.0004). No significant difference was observed in the time to stand and normal activity among drugs. A total of 66.7% of rats in the ET-26HCl group were evaluated to have mild hematuria. Then, etomidate and ET-26HCl had a milder blood pressure inhibition effect than propofol. Apnea was observed in all rats administered propofol and the duration for this side effect was 45.0 ± 9.0 s. For etomidate and ET-26HCl, no apnea was observed. No other clinical signs of side-effect were observed, and no rats died. No significant difference was observed in corticosterone concentrations between ET-26HCl and solvent group. However, rats administered etomidate had lower corticosterone concentrations than those administered ET-26HCl at 15, 30, and 60 min.
CONCLUSIONS
Our results indicate ET-26HCl in aged rats is an effective sedative-hypnotic with stable myocardial and respiratory performance and also have mild adrenocortical suppression. Thus, these findings increase the potential for the clinical use of ET-26HCl in the elderly population.
Topics: Aged; Male; Animals; Female; Rats; Humans; Etomidate; Propofol; Corticosterone; Rats, Sprague-Dawley; Anesthetics, Intravenous
PubMed: 36196398
DOI: 10.7717/peerj.13995 -
Molecules (Basel, Switzerland) Apr 2021Fatty acid amides are a diverse family of underappreciated, biologically occurring lipids. Herein, the methods for the chemical synthesis and subsequent characterization... (Review)
Review
Fatty acid amides are a diverse family of underappreciated, biologically occurring lipids. Herein, the methods for the chemical synthesis and subsequent characterization of specific members of the fatty acid amide family are described. The synthetically prepared fatty acid amides and those obtained commercially are used as standards for the characterization and quantification of the fatty acid amides produced by biological systems, a fatty acid amidome. The fatty acid amidomes from mouse NTG cells, sheep choroid plexus cells, , , and are presented.
Topics: Amides; Animals; Bees; Bombyx; Cell Line; Drosophila melanogaster; Fatty Acids; Lipids; Mice; Sheep; Tribolium
PubMed: 33925418
DOI: 10.3390/molecules26092543