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Journal of Neurology, Neurosurgery, and... Feb 1998
Topics: Acute Disease; Clinical Trials as Topic; Humans; Indoles; Migraine Disorders; Oxazoles; Oxazolidinones; Piperidines; Serotonin Receptor Agonists; Sumatriptan; Tryptamines
PubMed: 9489518
DOI: 10.1136/jnnp.64.2.143 -
Molecules (Basel, Switzerland) Dec 2022Benzoxazole and naphthoxazole fused systems are found in many biologically active molecules. Novel benzoxazole and naphthoxazole analogs functionalized by the...
Benzoxazole and naphthoxazole fused systems are found in many biologically active molecules. Novel benzoxazole and naphthoxazole analogs functionalized by the 2,4-dihydroxyphenyl moiety were designed, obtained and evaluated as a broad spectrum of biological potency compounds. Sulfinylbis[(2,4-dihydroxyphenyl)methanethione] or its analogs and 2-aminophenols or 1-amino-2-naphthol were used as starting reagents. 4-(Naphtho[1,2-][1,3]oxazol-2-yl)benzene-1,3-diol was identified as the most promising compound of the nanomolar activity against AChE (IC = 58 nM) of the mixed-type inhibition and of the moderate activity against BChE (IC = 981 nM). The higher antiproliferative potency against a panel of human cancer cell lines for naphtho[1,2-][1,3]oxazoles than for benzoxazoles was found. The activity of the analog with chlorine atom was in the range of 2.18-2.89 µM (IC) against all studied cells and it is similar to that of cisplatin studied comparatively. Moreover, this compound was not toxic at this concentration to human normal breast cells and keratinocytes. For some compounds it also has proved antioxidant properties at the level of IC = 0.214 µM, for the most active compound. The lipophilicity of all compounds, expressed as log values, is within the range recommended for potential drugs. The biological activity profile of the considered analogs and their lipophilic level justify the search for agents used in AD or in anticancer therapy in this group of compounds.
Topics: Humans; Benzoxazoles; Cholinesterase Inhibitors; Antioxidants; Structure-Activity Relationship; Oxazoles; Acetylcholinesterase; Molecular Docking Simulation; Molecular Structure
PubMed: 36500605
DOI: 10.3390/molecules27238511 -
Marine Drugs Jan 2010Calyculins, highly cytotoxic polyketides, originally isolated from the marine sponge Discodermia calyx by Fusetani and co-workers, belong to the lithistid sponges group.... (Review)
Review
Calyculins, highly cytotoxic polyketides, originally isolated from the marine sponge Discodermia calyx by Fusetani and co-workers, belong to the lithistid sponges group. These molecules have become interesting targets for cell biologists and synthetic organic chemists. The serine/threonine protein phosphatases play an essential role in the cellular signalling, metabolism, and cell cycle control. Calyculins express potent protein phosphatase 1 and 2A inhibitory activity, and have therefore become valuable tools for cellular biologists studying intracellular processes and their control by reversible phosphorylation. Calyculins might also play an important role in the development of several diseases such as cancer, neurodegenerative diseases, and type 2-diabetes mellitus. The fascinating structures of calyculins have inspired various groups of synthetic organic chemists to develop total syntheses of the most abundant calyculins A and C. However, with fifteen chiral centres, a cyano-capped tetraene unit, a phosphate-bearing spiroketal, an anti, anti, anti dipropionate segment, an alpha-chiral oxazole, and a trihydroxylated gamma-amino acid, calyculins reach versatility that only few natural products can surpass, and truly challenge modern chemists' asymmetric synthesis skills.
Topics: Animals; Enzyme Inhibitors; Humans; Marine Toxins; Organophosphates; Oxazoles; Protein Phosphatase 1; Protein Phosphatase 2; Species Specificity; Stereoisomerism
PubMed: 20161975
DOI: 10.3390/md80100122 -
Expert Opinion on Investigational Drugs Feb 2020: lipogenesis (DNL) plays a major role in fatty acid metabolism and contributes significantly to triglyceride accumulation within the hepatocytes in patients with... (Review)
Review
: lipogenesis (DNL) plays a major role in fatty acid metabolism and contributes significantly to triglyceride accumulation within the hepatocytes in patients with nonalcoholic steatohepatitis (NASH). Acetyl-CoA carboxylase (ACC) converts acetyl-CoA to malonyl CoA and is a rate-controlling step in DNL. Furthermore, malonyl-CoA is an important regulator of hepatic mitochondrial fat oxidation through its ability to inhibit carnitine palmitoyltransferase I. Therefore, inhibiting ACC pharmacologically represents an attractive approach to treating NASH.: This article summarizes preclinical and clinical data on the efficacy and safety of the liver-targeted ACC inhibitor GS-0976 (Firsocostat) for the treatment of NASH. In a phase 2 trial that included 126 patients with NASH and fibrosis, GS-0976 20 mg daily for 12 weeks showed significant relative reduction in liver fat by 29%; however, treatment was associated with an increase in plasma triglycerides with 16 patients having levels >500 mg/dL.: Preclinical and preliminary clinical data support the development of GS-0976 as treatment for NASH. ACC-induced hypertriglyceridemia can be mitigated by fish oil or fibrates, but the long-term cardiovascular effects require further investigations.
Topics: Acetyl-CoA Carboxylase; Animals; Drugs, Investigational; Enzyme Inhibitors; Fatty Acids; Humans; Isobutyrates; Lipogenesis; Non-alcoholic Fatty Liver Disease; Oxazoles; Pyrimidines; Triglycerides
PubMed: 31519114
DOI: 10.1080/13543784.2020.1668374 -
Current Opinion in Investigational... Apr 2005Bristol-Myers Squibb and Merck & Co are co-developing muraglitazar, a dual peroxisome proliferator-activated receptor-alpha/gamma agonist, for the potential treatment of... (Review)
Review
Bristol-Myers Squibb and Merck & Co are co-developing muraglitazar, a dual peroxisome proliferator-activated receptor-alpha/gamma agonist, for the potential treatment of type 2 diabetes and other metabolic disorders. In November 2004, approval was anticipated as early as mid-2005.
Topics: Animals; Drug Industry; Glycine; Humans; Hypoglycemic Agents; Oxazoles; PPAR alpha; PPAR gamma
PubMed: 15898350
DOI: No ID Found -
Journal of the American Chemical Society Nov 2019The enantioselective hydrocyanation of olefins represents a conceptually straightforward approach to prepare enantiomerically enriched nitriles. These, in turn, comprise...
The enantioselective hydrocyanation of olefins represents a conceptually straightforward approach to prepare enantiomerically enriched nitriles. These, in turn, comprise or are intermediates in the synthesis of many pharmaceuticals and their synthetic derivatives. Herein, we report a cyanide-free dual Pd/CuH-catalyzed protocol for the asymmetric Markovnikov hydrocyanation of vinyl arenes and the anti-Markovnikov hydrocyanation of terminal olefins in which oxazoles function as nitrile equivalents. After an initial hydroarylation process, the oxazole substructure was deconstructed using a [4 + 2]/retro-[4 + 2] sequence to afford the enantioenriched nitrile product under mild reaction conditions.
Topics: Alkenes; Catalysis; Nitriles; Oxazoles; Palladium; Stereoisomerism
PubMed: 31687821
DOI: 10.1021/jacs.9b10875 -
Scientific Reports Nov 2022Etoxazole is among the systemic pesticides with acaricidal and insecticidal characteristics. This paper reports the first evaluation of the toxic effects of Etoxazole on...
Etoxazole is among the systemic pesticides with acaricidal and insecticidal characteristics. This paper reports the first evaluation of the toxic effects of Etoxazole on Allium cepa L. Etoxazole solutions were applied to three groups formed from A. cepa bulbs at 0.125 mL/L, 0.25 mL/L and 0.5 mL/L doses, respectively. The control group was treated with tap water throughout the experimental period. The toxic effects of Etoxazole became more apparent as the dose of Etoxazole was increased. The growth-limiting effect was most pronounced in the highest dose group with approximately 29%, 70% and 58.5% reductions in germination percentage, root elongation and weight gain, respectively. The genotoxic effect of Etoxazole was most severe in the 0.5 mL/L dose group. In this group, the mitotic index decreased by 30% compared to the control group, while the micronucleus frequency increased to 45.3 ± 3.74. The most observed aberrations were fragment, vagrant chromosome, sticky chromosome, unequal distribution of chromatin, bridge, reverse polarization and nucleus with vacuoles. The malondialdehyde level showed a gradual increase with increasing Etoxazole doses and reached 2.7 times that of the control group in the 0.5 mL/L Etoxazole applied group. Catalase and Superoxide dismutase activities increased in the groups exposed to 0.125 mL/L and 0.25 mL/L Etoxazole with dose dependence and decreased abruptly in the group treated with 0.5 mL/L Etoxazole. Etoxazole triggered meristematic cell damages, such as epidermis cell damage, thickening of cortex cell walls, flattened cell nucleus and indistinct transmission tissue. Considering the versatile toxicity induced by Etoxazole, we announce that this chemical has the potential to cause serious damage to non-target organisms. It should be noted that the higher the dose of exposure, the more severe the level of damage. This study will be an important reminder to limit the indiscriminate use of this highly risky agrochemical.
Topics: Oxazoles; Risk Assessment; Oxidative Stress; Malondialdehyde
PubMed: 36443484
DOI: 10.1038/s41598-022-24966-0 -
Journal of the American Chemical Society Jul 2017We have recently shown that 2-aminoimidazole is a superior nucleotide activating group for nonenzymatic RNA copying. Here we describe a prebiotic synthesis of...
We have recently shown that 2-aminoimidazole is a superior nucleotide activating group for nonenzymatic RNA copying. Here we describe a prebiotic synthesis of 2-aminoimidazole that shares a common mechanistic pathway with that of 2-aminooxazole, a previously described key intermediate in prebiotic nucleotide synthesis. In the presence of glycolaldehyde, cyanamide, phosphate and ammonium ion, both 2-aminoimidazole and 2-aminooxazole are produced, with higher concentrations of ammonium ion and acidic pH favoring the former. Given a 1:1 mixture of 2-aminoimidazole and 2-aminooxazole, glyceraldehyde preferentially reacts and cyclizes with the latter, forming a mixture of pentose aminooxazolines, and leaving free 2-aminoimidazole available for nucleotide activation. The common synthetic origin of 2-aminoimidazole and 2-aminooxazole and their distinct reactivities are suggestive of a reaction network that could lead to both the synthesis of RNA monomers and to their subsequent chemical activation.
Topics: Aminoimidazole Carboxamide; Molecular Structure; Nucleotides; Oxazoles; Prebiotics
PubMed: 28640999
DOI: 10.1021/jacs.7b01562 -
Basic & Clinical Pharmacology &... Jul 2015In recent years, the spread of new psychoactive substances has dramatically increased in term of availability of both number of compounds and chemical families. In... (Review)
Review
In recent years, the spread of new psychoactive substances has dramatically increased in term of availability of both number of compounds and chemical families. In November 2012, 4,4'-Dimethylaminorex (4,4'-DMAR), a novel synthetic stimulant, was first detected in the Netherlands. Between June 2013 and June 2014, thirty-one deaths associated with the consumption of this new drug have been registered across Europe. In this MiniReview, we have summarized the chemical, pharmacological and toxicological information about this new legal high.
Topics: Animals; Cause of Death; Humans; Illicit Drugs; Oxazoles; Psychotropic Drugs; Risk Assessment; Substance-Related Disorders
PubMed: 25819702
DOI: 10.1111/bcpt.12399 -
Molecules (Basel, Switzerland) Aug 2020A search for potent antitubercular agents prompted us to design and synthesize sulfamethaoxazole incorporated 4-thiazolidinone hybrids (-) by using a cyclocondensation...
A search for potent antitubercular agents prompted us to design and synthesize sulfamethaoxazole incorporated 4-thiazolidinone hybrids (-) by using a cyclocondensation reaction between 4-amino--(5-methylisoxazol-3-yl)benzenesulfonamide (), aryl aldehyde (-), and mercapto acetic acid () resulting in good to excellent yields. All the newly synthesized 4-thiazolidinone derivatives were screened for their in vitro antitubercular activity against and ( strains. The compounds , , , , and revealed promising antimycobacterial activity against and strains with IC values in the range of 0.058-0.22 and 0.43-5.31 µg/mL, respectively. The most active compounds were also evaluated for their cytotoxicity against MCF-7, HCT 116, and A549 cell lines and were found to be non-cytotoxic. Moreover, the synthesized compounds were also analyzed for ADME (absorption, distribution, metabolism, and excretion) properties and showed potential as good oral drug candidates.
Topics: Antitubercular Agents; Cell Line, Tumor; Chemistry Techniques, Synthetic; Humans; Mycobacterium bovis; Mycobacterium tuberculosis; Oxazoles; Structure-Activity Relationship; Thiazolidines
PubMed: 32781534
DOI: 10.3390/molecules25163570