Abstract:
:Chiral inversion at a sulphoxide position of flosequinan enantiomers [(+/-)-7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone] occurred in conventional rats but not in either germ-free rats or rats treated with antibiotics after an oral administration of each enantiomer. Thus, it was postulated that the chiral inversion occurred by mechanisms mediated by intestinal bacteria. The intestinal content isolated from conventional rats reduced R(+)- and S(-)-flosequinan to produce the sulphide, while intestinal content from rats treated with antibiotics did not reduce the drug. Several strains of facultative anaerobes possessed a high flosequinan reducing activity. Escherichia coli, Klebsiella oxytoca and Klebsiella pneumoniae reduced R(+)-flosequinan to the sulphide stereoselectively. On the other hand, Enterobacter aerogenes and Micrococcus agilis exclusively reduced S(-)-flosequinan. The sulphide, which could be produced by intestinal bacteria from R(+)- and S(-)-flosequinan, was readily absorbed upon an oral administration to rats, and was oxidized fairly rapidly to R(+)- and S(-)-flosequinan and further to the sulphone form. Based on these data, it has been confirmed that chiral inversion at the sulphoxide position of flosequinan enantiomers occur via stereoselective reduction of sulphoxide by intestinal bacteria to form the sulphide, followed by oxidation of the sulphide in the body to produce R(+)- and S(-)-flosequinan.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Kashiyama E,Yokoi T,Todaka T,Odomi M,Kamataki Tdoi
10.1016/0006-2952(94)90093-0subject
Has Abstractpub_date
1994-07-19 00:00:00pages
237-43issue
2eissn
0006-2952issn
1873-2968pii
0006-2952(94)90093-0journal_volume
48pub_type
杂志文章abstract::The capacity of G protein-coupled receptors to modulate mechanistic target of rapamycin (mTOR) activity is a newly emerging paradigm with the potential to link cell surface receptors with cell survival. Cardiomyocyte viability is linked to signalling pathways involving Akt and mTOR, as well as increased glucose uptake...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2017.11.016
更新日期:2018-02-01 00:00:00
abstract::An important pathologic hallmark of Alzheimer's disease (AD) is neuroinflammation, a process characterized in AD by disproportionate activation of cells (microglia and astrocytes, primarily) of the non-specific innate immune system within the CNS. While inflammation itself is not intrinsically detrimental, a delicate ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2013.12.014
更新日期:2014-04-15 00:00:00
abstract::The possible role of fluroacetate in the toxicity and antitumour activity of the fluroethylnitrosoureas, BFNU and FCNU has been studied in CBA mice bearing the TLX5 lymphoma either sensitive (TLXS) or resistant (TLXRT) to nitrosoureas. Treatment of mice bearing either TLXS or TLXRT tumours with either BFNU or FCNU cau...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90353-3
更新日期:1985-09-15 00:00:00
abstract::Sorafenib is the only FDA approved drug for the treatment of advanced hepatocellular carcinoma (HCC) and other malignancies. Studies indicate that TGF-β signalling is associated with tumour progression in HCC. Autocrine and paracrine TGF-β promotes tumour growth and malignancy by inducing epithelial-mesenchymal transi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2018.04.014
更新日期:2018-08-01 00:00:00
abstract::For almost 10 years, Nod2 has been known as a cytosolic innate receptor able to sense peptidoglycan from Gram-positive and -negative bacteria and to trigger RIP2- and NF-κB-mediated pro-inflammatory and antibacterial response. Mutations in the gene encoding Nod2 in humans have been associated with Crohn's disease (CD)...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2010.07.016
更新日期:2010-12-15 00:00:00
abstract::Kidney cancer, also known as renal cell carcinoma (RCC), is one of the top 10 diagnosed cancers in the USA, and the incidence is rising. Despite major improvements in drug therapy strategies, RCC remains a deadly malignancy if not found and removed in its early stages. RCC is so highly drug-resistant that no effective...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2015.04.022
更新日期:2015-08-01 00:00:00
abstract::Transient outward potassium current (Ito) contributes to early repolarization of many mammalian cardiac action potentials, including human, whilst the rapid delayed rectifier K+ current (IKr) contributes to later repolarization. Fast Ito channels can be produced from the Shal family KCNDE gene product Kv4.3s, although...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2018.01.036
更新日期:2018-04-01 00:00:00
abstract::The purpose of this study was to investigate in rats the effects of three anthracyclines, pirarubicin, doxorubicin and epirubicin on gastric prostaglandin E2 (PGE2) metabolism and phospholipase A2 (PLA2, EC 3.1.1.4) activity. The level of the membrane precursor, arachidonic acid, and the stability of the membrane were...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90509-u
更新日期:1993-08-03 00:00:00
abstract::The use of either methadone or buprenorphine for treatment of the pregnant opiate-dependent patient improves maternal and neonatal outcome. However, patient outcomes are often complicated by neonatal abstinence syndrome (NAS). The incidence and severity of NAS should depend on opiate concentration in the fetal circula...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2009.07.002
更新日期:2009-11-01 00:00:00
abstract::Agonist-stimulated phosphoinositide metabolism plays a central role in pharmacomechanical coupling in airways smooth muscle (ASM). In many other tissues and cells, most noteably excitable cells, membrane depolarization or an increase in intracellular Ca2+ ([Ca2+]i) generated by inositol 1,4,5-trisphosphate (Ins(1,4,5)...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90252-6
更新日期:1994-06-15 00:00:00
abstract::Tumor cells are more sensitive to methionine restriction than normal tissues, a phenomenon known as methionine auxotrophy. Previous studies showed that 5-fluorouracil and methionine restriction act synergistically against a variety of tumors. The purpose of the current studies was to determine the molecular mechanism(...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(03)00406-4
更新日期:2003-09-01 00:00:00
abstract::We investigated the effect of aphidicolin, an inhibitor of DNA polymerase alpha and delta, on the induction of apoptosis by arabinosyl nucleosides in a human promyelocytic leukemia cell line, HL-60. Pretreatment of HL-60 cells with aphidicolin (2 microM) significantly increased the number of morphologically apoptotic ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90631-6
更新日期:1993-12-03 00:00:00
abstract::The long-term effects of incubating freshly isolated, elicited guinea-pig peritoneal macrophages with the beta-adrenoceptor agonist isoprenaline and the selective inhibitor of phosphodiesterase (PDE) IV rolipram, on adenosine-3',5'-cyclic phosphate (cAMP)-specific PDE IV activity have been investigated. The level of c...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)02104-3
更新日期:1995-12-22 00:00:00
abstract::Thiazolidinediones (also referred to as glitazones), agonists for Peroxisome Proliferator-Activated Receptor gamma (PPARγ), are used for treating type 2 diabetes mellitus, where they decrease insulin resistance and cardiovascular risk. Compounds bearing the thiazolidinedione structure have also been shown to inhibit p...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2012.11.013
更新日期:2013-02-15 00:00:00
abstract::We have recently reported evidence that a simple beta-linked alkylated mannose reversibly increased the magnitude of GABA(A) receptor currents evoked in cultured rat pyramidal neurons whilst concomitantly reducing the incidence of spontaneous synaptic activity. In this present study, the effects of the simple beta-lin...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(02)01611-8
更新日期:2003-02-15 00:00:00
abstract::Arylamine N-acetyltransferase 1 (NAT1) conjugates several aromatic amines and their N-hydroxylated metabolites by N- or O-acetylation. NAT1 genotype and phenotype is known to be variable in human populations. In this study, we set out to measure the functional relevance of the frequent NAT1 gene variants for the activ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00269-5
更新日期:1999-12-01 00:00:00
abstract::The protective action of cysteine or mercaptopropionylglycine (MPG) in acute ethanol-induced liver injury has been investigated in the rat. Cysteine accelerated clearance of ethanol and acetaldehyde from blood and liver and prevented an increase in hepatic content of triglyceride and serum ornithine carbamoyl transfer...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90562-2
更新日期:1983-01-15 00:00:00
abstract::Diabetic nephropathy (DN) is one of the most prevalent lethal complications of diabetes that leads to end stage renal disease. Although several clinical approaches exist to attenuate DN, there is not curative treatment to date. DN is complicated, as it involves several simultaneous molecular pathways. Some natural and...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2018.06.017
更新日期:2018-09-01 00:00:00
abstract::Prunetin is an O-methylated isoflavone, which is a type of flavonoid. There are a limited number of reports detailing the biological activities of prunetin. Although an anti-inflammatory effect of prunetin has been reported in vitro, to our knowledge, there have been no reports on anti-adipogenic effects of prunetin i...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.02.020
更新日期:2013-05-15 00:00:00
abstract::In eukaryotic cells, the DNA molecule is found in the form of a nucleoprotein complex named chromatin. The basic unit of the chromatin is the nucleosome, which comprises 147 base pairs of DNA wrapped around an octamer of core histones (made of two molecules of each H2A, H2B, H3, and H4 histones). Each nucleosome is li...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2006.06.016
更新日期:2006-11-30 00:00:00
abstract::Curcumin (diferuoylmethane), the yellow pigment in the rhizome of tumeric (Curcuma longa), an ingredient of curry spice, is known to exhibit a variety of pharmacological effects including antitumor, antiinflammatory, and antiinfectious activities. Although its precise mode of action remains elusive, curcumin has been ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(97)00251-7
更新日期:1997-10-15 00:00:00
abstract::To uncover the full spectrum of its pharmacological activities, the selective COX-2 inhibitor celecoxib is routinely being used at concentrations of up to 100 microM in cell culture. At these elevated concentrations, several COX-2-independent effects were identified, although many details of these events have remained...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2007.08.029
更新日期:2008-01-15 00:00:00
abstract::Cobalt protoporphyrin generated from 5-amino[4-14C]laevulinate by homogenates or primary cultures of chick embryo liver exposed to CoCl2 was found to be radioactivity unextractable by acid/acetone, when extra protein was added. The activity of ferrochelatase was required for formation of cobalt protoporphyrin since in...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90333-1
更新日期:1982-03-15 00:00:00
abstract::To study the effect of growth factors on iatrogenic apoptosis, we examined the influence of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) on staurosporine-induced apoptosis in primary cultures of human umbilical vein endothelial cells (HUVEC). Apoptosis was evaluated by a cell viability t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2003.09.007
更新日期:2004-01-15 00:00:00
abstract::Glyburide is a second-generation sulfonylurea hypoglycemic drug used for the treatment of select women with pregestational and gestational diabetes mellitus (GDM). In vitro and in vivo investigations demonstrated its very low transplacental transfer to the fetal circulation. However, the factors influencing its low tr...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.05.019
更新日期:2006-08-28 00:00:00
abstract::The effects of beta 1- and beta 1 + beta 2-antagonists on the myocardial adaptation to exercise training were investigated in male Sprague-Dawley rats randomly divided into trained (treadmill, 1 hr/day, 5 days/week for 10 weeks at 27 m/min, 15% grade) without drug (TC), sedentary without drug (SC), trained treated wit...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90319-4
更新日期:1987-10-15 00:00:00
abstract::We tested the ability of a wide variety of organic compounds, including benzene and phenol derivatives, aromatic amines, pyrazoline derivatives and other non-steroidal anti-inflammatory drugs, to act as cosubstrates during the horseradish peroxidase/hydrogen peroxide-mediated oxygenation of arachidonic acid. Structura...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90326-2
更新日期:1989-04-15 00:00:00
abstract::Cathepsin K is a cysteine protease that degrades type I human collagen during bone resorption. We have expressed the recombinant human cathepsin K in Chinese hamster ovary (CHO) cells as a pre-proenzyme and demonstrated that it is processed intracellularly to an active enzyme form and that only the proenzyme form is s...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(00)00381-6
更新日期:2000-09-15 00:00:00
abstract::We have investigated a series of novel 4-aminoquinoline analogues related to amodiaquine, that possess side chain modifications designed to influence both drug pKa and lipophilicity. These compounds have been used to determine the influence of physicochemical properties on antimalarial activity against, and accumulati...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(96)00354-1
更新日期:1996-09-13 00:00:00
abstract::gamma-Aminobutyric acid (GABA) uptake was studied in bovine chromaffin cells maintained in primary culture. Uptake was found to be dependent on Na+, but not on K+ and Ca2+ ions; it was found that 2 Na+ ions were necessary for each molecule of GABA transported. 2,4-Dinitrophenol, ouabain and vanadate inhibited GABA upt...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90459-0
更新日期:1989-07-15 00:00:00