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Applied Biochemistry and Biotechnology Dec 2013Some series of arylidene barbiturates and thiobarbiturates were evaluated for their antibacterial, antioxidant, and urease inhibition activities. The arylidene...
Some series of arylidene barbiturates and thiobarbiturates were evaluated for their antibacterial, antioxidant, and urease inhibition activities. The arylidene barbiturates and thiobarbiturates were tested for antimicrobial activity using the agar well diffusion technique against 13 bacteria. The synthesized compounds (1a-g) were screened for antiurease and antioxidant activities. The results showed that the synthesized compounds (1a-g) had effective antiurease, antioxidant, and antibacterial activities.
Topics: Anti-Bacterial Agents; Antioxidants; Bacteria; Barbiturates; Microbial Sensitivity Tests; Oxidation-Reduction; Thiobarbiturates; Urease
PubMed: 24018846
DOI: 10.1007/s12010-013-0486-6 -
Minerva Anestesiologica May 2022
Topics: Adult; Barbiturates; Coma; Craniocerebral Trauma; Glasgow Coma Scale; Humans; Intracranial Hypertension; Intracranial Pressure
PubMed: 34709022
DOI: 10.23736/S0375-9393.21.16180-2 -
ChemMedChem Dec 2016The development of novel thalidomide derivatives as immunomodulatory and anti-angiogenic agents has revived over the last two decades. Herein we report the design and...
The development of novel thalidomide derivatives as immunomodulatory and anti-angiogenic agents has revived over the last two decades. Herein we report the design and synthesis of three chemotypes of barbituric acids derived from the thalidomide structure: phthalimido-, tetrafluorophthalimido-, and tetrafluorobenzamidobarbituric acids. The latter were obtained by a new tandem reaction, including a ring opening and a decarboxylation of the fluorine-activated phthalamic acid intermediates. Thirty compounds of the three chemotypes were evaluated for their anti-angiogenic properties in an ex vivo assay by measuring the decrease in microvessel outgrowth in rat aortic ring explants. Tetrafluorination of the phthalimide moiety in tetrafluorophthalimidobarbituric acids was essential, as all of the nonfluorinated counterparts lost anti-angiogenic activity. An opening of the five-membered ring and the accompanying increased conformational freedom, in case of the corresponding tetrafluorobenzamidobarbituric acids, was well tolerated. Their activity was retained, although their molecular structures differ in torsional flexibility and possible hydrogen-bond networking, as revealed by comparative X-ray crystallographic analyses.
Topics: Angiogenesis Inhibitors; Animals; Aorta; Barbiturates; Crystallography, X-Ray; Molecular Conformation; Phthalimides; Rats; Structure-Activity Relationship; Thalidomide
PubMed: 27805767
DOI: 10.1002/cmdc.201600496 -
Neurocritical Care Feb 2011Refractory status epilepticus (RSE) has a mortality of 16-39%; coma induction is advocated for its management, but no comparative study has been performed. We aimed to... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Refractory status epilepticus (RSE) has a mortality of 16-39%; coma induction is advocated for its management, but no comparative study has been performed. We aimed to assess the effectiveness (RSE control, adverse events) of the first course of propofol versus barbiturates in the treatment of RSE.
METHODS
In this randomized, single blind, multi-center trial studying adults with RSE not due to cerebral anoxia, medications were titrated toward EEG burst-suppression for 36-48 h and then progressively weaned. The primary endpoint was the proportion of patients with RSE controlled after a first course of study medication; secondary endpoints included tolerability measures.
RESULTS
The trial was terminated after 3 years, with only 24 patients recruited of the 150 needed; 14 subjects received propofol, 9 barbiturates. The primary endpoint was reached in 43% in the propofol versus 22% in the barbiturates arm (P = 0.40). Mortality (43 vs. 34%; P = 1.00) and return to baseline clinical conditions at 3 months (36 vs. 44%; P = 1.00) were similar. While infections and arterial hypotension did not differ between groups, barbiturate use was associated with a significantly longer mechanical ventilation (P = 0.03). A non-fatal propofol infusion syndrome was detected in one patient, while one subject died of bowel ischemia after barbiturates.
DISCUSSION
Although undersampled, this trial shows significantly longer mechanical ventilation with barbiturates and the occurrence of severe treatment-related complications in both arms. We describe practical issues necessary for the success of future studies needed to improve the current unsatisfactory state of evidence.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Barbiturates; Coma; Critical Care; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Propofol; Prospective Studies; Status Epilepticus; Treatment Outcome; Young Adult
PubMed: 20878265
DOI: 10.1007/s12028-010-9445-z -
Anesthesiology Sep 1977
Review
Topics: Anesthesia; Animals; Barbiturates; Brain; Brain Edema; Craniocerebral Trauma; Humans; Hyperventilation; Hypotension; Hypothermia, Induced; Hypoxia, Brain; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient
PubMed: 329713
DOI: 10.1097/00000542-197709000-00010 -
Acta Poloniae Pharmaceutica 2009Hydrolysis of 2,4-dithiophenobarbital in aqueous solutions of pH 2-12 was investigated at 40 and 60 degrees C using UV spectrophotometry. The values of reaction order,...
Hydrolysis of 2,4-dithiophenobarbital in aqueous solutions of pH 2-12 was investigated at 40 and 60 degrees C using UV spectrophotometry. The values of reaction order, rate constants, pKa1 and pKa2 and activation energy were determined. The preliminary estimation of degradation products was accomplished using thin layer chromatography. The major products were isolated by circular chromatography and identified by spectroscopic and classical methods.
Topics: Barbiturates; Buffers; Chromatography, Thin Layer; Hydrolysis; Kinetics; Phenobarbital; Solvents; Spectrophotometry, Ultraviolet
PubMed: 19719044
DOI: No ID Found -
Postgraduate Medical Journal Mar 1977An infant with neonatal barbiturate withdrawal syndrome is reported. The clinical features, diagnosis and treatment of this condition are discussed. A retrospective...
An infant with neonatal barbiturate withdrawal syndrome is reported. The clinical features, diagnosis and treatment of this condition are discussed. A retrospective review of fifty-three infants of barbiturate-treated epileptic mothers indicated a high incidence of "jitteriness" (17%) and feeding problems (36%) in the immediate neonatal period.
Topics: Adult; Barbiturates; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Maternal-Fetal Exchange; Pregnancy; Substance Withdrawal Syndrome
PubMed: 870892
DOI: 10.1136/pgmj.53.617.157 -
Yakugaku Zasshi : Journal of the... Jan 2005Thirty-six allyl substituted oxopyrimidine analogues such as barbituric acid (BA), barbiturates, uracil, thymine, and related derivatives including 13 new compounds were... (Review)
Review
[Studies on the structure-activity relationship of allyl substituted oxopyrimidines searching for the novel antagonist or agonist of barbiturates to the sleep mechanism based on the uridine receptor theory--barbituric acid to uridine (part I)].
Thirty-six allyl substituted oxopyrimidine analogues such as barbituric acid (BA), barbiturates, uracil, thymine, and related derivatives including 13 new compounds were synthesized and their pharmacologic effects ([hypnotic activity, anticonvulsant activity against pentylentetrazol (PTZ)-induced seizures, and LD(50)]) and interactions with the barbiturates were evaluated in mice and rats. The results are briefly and parially summarized as follows. BA prolonged pentobarbital (PB)-induced sleep and had some central depressant effects. N,5,5-triallyl-BA exhibited some hypnotic and anticonvulsant activities, although the other 5,N-allyl-compounds did not show any activity except for allobarbital (AlloB). N-allyl-BA, 5-allyl-BA, N(1),N(3),5-triallyl-BA, N,5,5-triallyl-BA, and N(1),N(3),5,5-tetraallyl-BA also prolonged PB-induced sleep. Interestingly, N,5,5-triallyl-BA was the most potent in the interaction with AlloB, phenobarbital (PheB), amobarbital (AB), PB, and thiopental (TP) but not barbital (B). N(1),N(3),5,5-tetraallyl-BA prolonged AlloB-, PB-, and AB-induced sleep but not B-, PheB-, and TP-induced sleep. N(1),N(3),5-triallyl-B prolonged only PB- and TP-induced sleep. 5,5-diallyl-BA prolonged PheB- and TP-induced sleep. N,5-diallyl-BA prolonged only TP-induced sleep. In contrast, BA and N(1),N(3),5-triallyl-AB tended to antagonize AlloB, AB, and B. N(1),N(3),5,5-tetraallyl-BA also slightly antagonized B, PheB, and TP. 5,5-diallyl-BA antagonized only AB. The prolonging effects of BA, N,5,5-triallyl-BA, and N(1),N(3),5,5-tetraallyl-BA on PB-induced sleep were dose dependent. These results indicate that the position and number of allyl groups substituted on the structure of BA play an important role in their depressant activities. This review deals with the structure-activity relationship of allyl-substituted oxopyrimidines as part of our search for antagonists and agonists of barbiturates as well as their mechanisms of action.
Topics: Animals; Antidepressive Agents; Barbiturates; Central Nervous System Depressants; Dose-Response Relationship, Drug; Humans; Hypnotics and Sedatives; Mice; Rats; Sleep; Structure-Activity Relationship; Uridine
PubMed: 15635282
DOI: 10.1248/yakushi.125.73 -
Anaesthesia Jul 1982
Topics: Anesthesia, Intravenous; Anesthetics; Barbiturates; Germany; Hexobarbital; History, 19th Century; History, 20th Century; Methohexital; Thiobarbiturates; Thiopental; United States
PubMed: 7048989
DOI: 10.1111/j.1365-2044.1982.tb01310.x -
PloS One 2012Barbiturates potentiate GABA actions at the GABA(A) receptor and act as central nervous system depressants that can induce effects ranging from sedation to general...
Barbiturates potentiate GABA actions at the GABA(A) receptor and act as central nervous system depressants that can induce effects ranging from sedation to general anesthesia. No structural information has been available about how barbiturates are recognized by their protein targets. For this reason, we tested whether these drugs were able to bind specifically to horse spleen apoferritin, a model protein that has previously been shown to bind many anesthetic agents with affinities that are closely correlated with anesthetic potency. Thiopental, pentobarbital, and phenobarbital were all found to bind to apoferritin with affinities ranging from 10-500 µM, approximately matching the concentrations required to produce anesthetic and GABAergic responses. X-ray crystal structures were determined for the complexes of apoferritin with thiopental and pentobarbital at resolutions of 1.9 and 2.0 Å, respectively. These structures reveal that the barbiturates bind to a cavity in the apoferritin shell that also binds haloalkanes, halogenated ethers, and propofol. Unlike these other general anesthetics, however, which rely entirely upon van der Waals interactions and the hydrophobic effect for recognition, the barbiturates are recognized in the apoferritin site using a mixture of both polar and nonpolar interactions. These results suggest that any protein binding site that is able to recognize and respond to the chemically and structurally diverse set of compounds used as general anesthetics is likely to include a versatile mixture of both polar and hydrophobic elements.
Topics: Anesthetics; Animals; Apoferritins; Barbiturates; Binding Sites; Crystallography, X-Ray; Horses; Pentobarbital; Protein Binding; Thiopental
PubMed: 22359658
DOI: 10.1371/journal.pone.0032070