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 accumulation by, both chloroquine-susceptible and chloroquine-resistant isolates of Plasmodium falciparum. The compounds tested exhibited a 500-fold range of absolute antimalarial potency. Absolute drug potency and drug accumulation were found to be significantly correlated in each of the four isolates of Plasmodium falciparum studied. The level of accumulation was unrelated to lipophilicity and was significantly greater than the predicted levels of accumulation based on drug pKa, compartmental pH, and Henderson-Hasselbach considerations. Further analysis of the relationship between 4-aminoquinoline accumulation and activity implicated the involvement of additional forces in the accumulation process.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Hawley SR,Bray PG,O'Neill PM,Park BK,Ward SAdoi
10.1016/0006-2952(96)00354-1subject
Has Abstractpub_date
1996-09-13 00:00:00pages
723-33issue
5eissn
0006-2952issn
1873-2968pii
0006-2952(96)00354-1journal_volume
52pub_type
杂志文章abstract：:Polyamines (putrescine, spermidine and spermine) are aliphatic amines that are produced by the action of ornithine decarboxylase (ODC) in a rate-limiting and protein kinase C (PKC)-regulated step. Because high levels of polyamines are found in the synovial fluid of arthritic patients, the aim of the present study was ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.04.015
更新日期：2011-08-01 00:00:00
abstract：:This study reports an investigation on the effect of the seleno-organic compound ebselen on rat liver mitochondria. We show that low concentrations of ebselen induced an increase in rat liver mitochondrial membrane permeability, resulting in swelling and loss of membrane potential. These effects were mediated by the o...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00114-x
更新日期：2003-05-15 00:00:00
abstract：:Adiponectin blocks hepatocellular carcinoma (HCC) progression by inducing cell apoptosis through the modulation of C-Jun N-terminal kinase and mammalian target of rapamycin. However, the precise upstream signaling pathways or molecules remain elusive. In the present study, we analyzed the role of antioxidant protein t...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2014.12.001
更新日期：2015-01-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(96)00417-0
更新日期：1996-10-11 00:00:00
abstract：:The dithiol-reducing thioredoxin/thioredoxin reductase system normally maintains the reduced state of key enzymes responsible for the cell's anti-oxidant defences. We therefore addressed the question of whether AW 464--a novel thioredoxin inhibitor--as well as broad spectrum dithiol ligands diamide and phenylarsine ox...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00471-4
更新日期：2003-11-01 00:00:00
abstract：:Administration of pentylenetetrazol (PTZ) (60 mg/kg, s.c.) to normal or carbaryl (200 mg/kg, p.o.) treated adult male albino rats produced characteristic changes in the steady-state levels of striatal dopamine (DA), noradrenaline (NA) and homovanillic acid (HVA) at different time intervals (0.5, 1.0 and 2.0 hr). The e...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90189-3
更新日期：1985-02-15 00:00:00
abstract：:Oral administration of tobacco to rats for 21 days caused remarkable stimulation of the metabolism of phenacetin, aniline and benzo[a]pyrene, a carcinogen, by hepatic microsomal mixed function oxidases (MFO). Such treatment for 6 days resulted in a small increase in the activities of phenacetin O-dealkylase and aromat...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90386-0
更新日期：1982-04-15 00:00:00
abstract：:HOE 731, a substituted thienoimidazole derivative, was studied on [14C] aminopyrine uptake and oxygen consumption in isolated rabbit gastric glands. HOE 731 caused a concentration-dependent inhibition of [14C]aminopyrine uptake during histamine and dbcAMP stimulation. The inhibition during dbcAMP stimulation was in ac...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90360-w
更新日期：1990-10-15 00:00:00
abstract：:The hypolipidemic drug ethyl chlorophenoxyisobutyrate (clofibrate) is known to induce peroxisome proliferation and to be carcinogenic after long term administration to rats and mice. We examined the effects of treatment with this drug for periods of up to 18 months on cytosolic ATP-stimulated and ADP-inhibited acetyl-...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90038-x
更新日期：1993-04-06 00:00:00
abstract：:Tumor necrosis factor (TNF) is a pleiotropic cytokine that mediates different cellular responses including cytotoxicity, cytostasis, proliferation, differentiation and expression of specific genes. Recent studies have demonstrated that chemotherapeutic drugs that inhibit the nuclear enzyme DNA topoisomerase II synergi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90468-c
更新日期：1993-10-05 00:00:00
abstract：:Sulphate conjugation was investigated using extracts of human foetal liver cells in culture. The three reactions which are involved in sulphate conjugation were measured singly or in combination: they are (i) the PAPS generation catalyzed by ATP-sulphurylase and adenosine 5'-phosphosulphate (APS)-kinase, (ii) the phen...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90331-0
更新日期：1988-12-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2008.08.014
更新日期：2008-11-15 00:00:00
abstract：:Isolated rat liver mitochondria have been incubated in the presence of the general anesthetic 2,6-diisopropylphenol (0-100 microM) and the efficiency of oxidative phosphorylation has been evaluated by measuring the respiratory rates, the rates of ATP synthesis or hydrolysis and the magnitude of the transmembrane elect...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90684-w
更新日期：1991-06-21 00:00:00
abstract：:The influence of both short- and long-term ethanol exposure on the lipid metabolism was determined in the human hepatoma cell line HepG2. Ethanol did not cause any cytotoxicity or lipid peroxidation even after 7 days of 100 mM ethanol treatment of HepG2 cells. Incubation of cells in the presence of [1-(14)C]ethanol de...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)00896-1
更新日期：2002-04-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2005.04.040
更新日期：2005-07-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(96)00358-9
更新日期：1996-09-13 00:00:00
abstract：:The development of the plasma cell tumor (PCT) model was the first widely accepted in vivo model of multiple myeloma (MM). Potter and colleagues used this chemically induced PCT model to study the pathophysiology of malignant plasma cells and also used it to screen anti-MM agents. Two decades later the C57BL/KaLwRij m...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2014.03.013
更新日期：2014-06-01 00:00:00
abstract：:Several derivatives of N-t-butyl-alpha-phenylnitrone (PBN) such as N-2-(2-ethoxycarbonyl-propyl)-alpha-phenylnitrone (EPPN) have recently been reported to form superoxide spin adducts (t(1/2) ca. 2-7 min at pH 7.0), which are considerably more stable than their respective PBN or DMPO adducts (t(1/2) ca. 10 and 45 s, r...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.03.017
更新日期：2004-07-01 00:00:00
abstract：:Current epidemiological and experimental studies support a beneficial role of dietary polyphenols in several gastrointestinal diseases, including inflammatory bowel disease. The aim of this study was to gain a better understanding of the effects of a naturally occurring polyphenol, ellagic acid, present in some fruits...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.06.043
更新日期：2011-10-01 00:00:00
abstract：:Although it is generally believed that thiazolidinediones ameliorate insulin resistance by lowering circulating free fatty acids, direct effects of these drugs in skeletal muscle may also contribute to their antidiabetic action. We report that troglitazone administration to mice for 1 day increased the protein express...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2005.01.015
更新日期：2005-04-15 00:00:00
abstract：:Male weanling F-344 rats were maintained on selenium-supplemented or -deficient diets and were exposed to fresh cigarette smoke daily for 28 weeks. The deficient status of animals was demonstrated by a significant reduction in the pulmonary and hepatic glutathione peroxidase (GSH-Px) activity of rats on selenium-defic...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90471-5
更新日期：1986-07-15 00:00:00
abstract：:Stimulation of lipolysis in murine adipocytes in response to a lipid-mobilizing factor produced by a cachexia-inducing murine adenocarcinoma was inhibited by eicosapentaenoic acid (EPA) with a Ki value of 104 microM. The inhibitory effect was strictly structurally specific, since other related fatty acids of both the ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90016-x
更新日期：1991-01-01 00:00:00
abstract：:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is believed to induce neurotoxicity by inhibiting mitochondrial oxidative metabolism, whereas acetyl-L-carnitine (ALC) facilitates this process by transporting fatty acids into mitochondria for beta oxidation. We investigated whether large doses of ALC given by gavag...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90034-t
更新日期：1993-05-25 00:00:00
abstract：:Metabolomics offers the opportunity to uncover endogenous biomarkers that can lead to metabolic pathways and networks and that underpin drug toxicity mechanisms. A novel protocol is presented and discussed that is applicable to drugs which generate urinary metabolites when administered to mice sensitive to its toxicit...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2018.09.022
更新日期：2018-10-01 00:00:00
abstract：:5-Lipoxygenase (5-LO) is a crucial enzyme of the arachidonic acid (AA) cascade and catalyzes the formation of bioactive leukotrienes (LTs) which are involved in inflammatory diseases and allergic reactions. The pathophysiological effects of LTs are considered to be prevented by 5-LO inhibitors. In this study we presen...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.10.012
更新日期：2012-01-15 00:00:00
abstract：:Taxol-induced mitotic block and apoptosis were investigated using taxol-sensitive human leukemia HL-60 cells at submicromolar concentrations of the drug. Cells exposed to either 20 nM taxol for 1 hr or 10 nM taxol for 12 hr were able to resume normal growth, whereas cells exposed to 60 nM taxol for 1 hr or 10 nM taxol...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)82450-1
更新日期：1997-06-01 00:00:00
abstract：:Thioredoxin reductase (TR1) is a selenoprotein that is involved in cellular redox status control and deoxyribonucleotide biosynthesis. Many cancers, including lung, overexpress TR1, making it a potential cancer therapy target. Previous work has shown that TR1 knockdown enhances the sensitivity of cancer cells to antic...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.09.024
更新日期：2011-01-15 00:00:00
abstract：:Resistance to some (lipophilic) antifolates has been associated with P-glycoprotein (P-gp)-mediated multidrug resistance (MDR). A possible relationship with non-P-gp MDR has not been established. We studied resistance to antifolates in SW-1573 human lung carcinoma cells, a P-gp overexpressing variant SW-1573/2R160 and...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)82448-3
更新日期：1997-06-15 00:00:00
abstract：:Paraquat and the structurally similar polyamines, such as putrescine and spermidine, are accumulated actively and selectively by the alveolar type II cells via the polyamine uptake system. We report the uptake kinetics of paraquat and putrescine and their mutual inhibition in freshly isolated rat type II cell suspensi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90364-o
更新日期：1992-09-25 00:00:00
abstract：:Naproxen, a non-steroidal anti-inflammatory drug, is known to be highly effective and relatively safe, but some side-effects in the liver have been reported. In the present study, the effect of naproxen metabolism on rat liver microsomes was studied by determining lipid peroxidation in terms of thiobarbituric acid rea...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90315-n
更新日期：1993-04-22 00:00:00
