Abstract:
:Only a few biosynthetic pathways in fungal cells have been used as antifungal targets. Therefore, the number of antifungals has been limited, and a cross-drug resistance among them has emerged in the therapy of mycoses. Under such circumstances, the identification of an antifungal with a new mode of action is highly desirable. By infecting mice with a mutant of C. albicans deficient in the sulfate assimilation pathway, we have discovered a new target for the discovery of antifungal agents. We have proven that azoxybacilin inhibits the sulfate assimilation pathway by showing its inhibitory activity for [35S]SO4 incorporation into proteins. We have also demonstrated that azoxybacilin was taken up into fungal cells via an active transport system specific for methionine. This sharing of the uptake system with methionine may explain the mechanism by which the antifungal activity of azoxybacilin is antagonized by methionine, and led us to design azoxybacilin derivatives that lack the structural feature of amino acids and, at the same time, have increased hydrophobicity to give higher non-specific permeability through the cell membrane. As a result, we have found that ester derivatives of azoxybacilin were not antagonized by methionine in their uptake, and that they showed antifungal activity independent of methionine. The benzyl ester of azoxybacilin was the same as azoxybacilin in its mode of action, but was not markedly antagonized by methionine at concentrations up to 1 mg/ml. These results suggest that azoxybacilin may not merely interfere with the sulfate assimilation pathway.
journal_name
Biol Pharm Bulljournal_title
Biological & pharmaceutical bulletinauthors
Aoki Y,Kamiyama T,Fujii T,Yamamoto M,Ohwada J,Arisawa Mdoi
10.1248/bpb.18.1267subject
Has Abstractpub_date
1995-09-01 00:00:00pages
1267-71issue
9eissn
0918-6158issn
1347-5215journal_volume
18pub_type
杂志文章abstract::The effects of conjugated linoleic acid (CLA) against anaphylaxis and allergic pruritus were investigated using a in vivo assay. Inhibitory effects of CLA were observed on the immediate (type 1) hypersensitivity reaction, with CLA significantly suppressing the decrease in blood pressure (BP) and blood flow (BF) induce...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.25.1655
更新日期:2002-12-01 00:00:00
abstract::Carvedilol, an alpha- and beta-adrenergic blocking drug, is mainly metabolized by CYP2D6, UGT1A1, UGT2B4 and UGT2B7. This drug is administered orally as a racemic mixture of R(+)- and S(-)-enantiomers. It has been reported that CYP2D6 prefers metabolizing S-carvedilol to R-carvedilol stereoselectively. On the other ha...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.30.2146
更新日期:2007-11-01 00:00:00
abstract::The effects of nefiracetam on the cerebral adenylyl cyclase (AC) activity of animals with microsphere embolism-induced memory dysfunction were examined. Sustained cerebral ischemia in the right cerebral hemisphere was induced by an injection of microspheres into the right internal carotid artery of rats. To examine le...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.26.318
更新日期:2003-03-01 00:00:00
abstract::We determined the in vivo and in vitro antitumor activities of gambogic acid (GA) and one of the possible mechanisms for its inhibitory activities. In vivo antitumor activity of GA was evaluated by the relative tumor growth ratio (T/C) in nude mice, and in vitro inhibition of SPC-A1 cells was measured by 3-(4,5-dimeth...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.27.1769
更新日期:2004-11-01 00:00:00
abstract::The mechanistic/mammalian target of rapamycin complex-1 (mTORC1) integrates multiple signaling pathways and regulates various cellular processes. Tuberous sclerosis complex 1 (Tsc1) and complex 2 (Tsc2) are critical negative regulators of mTORC1. Mouse genetic studies, including ours, have revealed that inactivation o...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b20-00619
更新日期:2020-01-01 00:00:00
abstract::We examined the transport mechanisms of daunorubicin (DNR) and doxorubicin (ADR) in HL60 and HL60/THP cells which were the non-P-glycoprotein-mediated resistant clone of the parent HL60 cells and showed a low degree of resistance, and compared them with those of pirarubicin (THP). In both lines, it appeared that the u...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.19.100
更新日期:1996-01-01 00:00:00
abstract::The pharmacological characteristics of Ryokan-kyomi-shinge-nin-to (RKS), a traditional oriental herbal (Kampo) medicine which has been used for the treatment of allergic asthma and rhinitis, were investigated. The number of sneezes by actively sensitized mice after a topical antigen challenge was significantly reduced...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.25.1562
更新日期:2002-12-01 00:00:00
abstract::Topiramate pharmacokinetics is influenced by individual factors such as patient age, renal function and co-treatment. The aim of this study was to develop a population pharmacokinetic model of topiramate to assist dosage adjustments in individual patients. Steady-state topiramate plasma concentrations in patients with...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.33.1176
更新日期:2010-01-01 00:00:00
abstract::Radiation induces an important inflammatory response in the irradiated organs, characterized by leukocyte infiltration and vascular changes. Since adhesion molecules play an important role in facilitating the immune response at the inflammation sites, interfering with the expression of these molecules may be an import...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.33.752
更新日期:2010-01-01 00:00:00
abstract::A liposomal formulation of UCN-01 was studied to prevent binding of drug to human alpha1-acid glycoprotein (hAGP). The release of drug from liposomes added to various media was investigated by monitoring the concentration of UCN-01 in different fractions. Protein bound UCN-01 was separated from liposomal UCN-01 and fr...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.28.1259
更新日期:2005-07-01 00:00:00
abstract::Hypertension is one of the most prevalent diseases worldwide and can cause harmful complications within the vascular system. Further research on vascular responsiveness to different ligands and diverse receptors in various arteries is required to understand the mechanisms underlying the development of these vascular c...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b17-00987
更新日期:2018-01-01 00:00:00
abstract::Osthole, a main active constituent from Cnidium monnieri (L.) CUSSON, has been considered therapeutic agent in the treatment of ischemic stroke. This study was designed to investigate the effect of osthole on permanent middle cerebral artery occlusion (MCAO) in rats. Osthole was administrated by gavage to the normal a...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b12-00133
更新日期:2012-01-01 00:00:00
abstract::Di-n-butyl phthalate (DBP), a phthalate ester, has been shown to have an adjuvant effect on fluorescein isothiocyanate (FITC)-induced contact hypersensitivity (CHS) mouse models. Di-n-butyl maleate (DBM), widely used as a plasticizer for industrial application, has been reported to cause dermatitis in humans. DBM is a...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b15-00683
更新日期:2016-01-01 00:00:00
abstract::Plasma hyaluronan biding protein (PHBP) is a novel serine protease, which has an amino acid sequence homology to that of hepatocyte growth factor activator (HGFA), and has a similar domain structure to that of urinary plasminogen activator (u-PA), found in human plasma. We searched the PHBP substrate in human plasma b...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.24.140
更新日期:2001-02-01 00:00:00
abstract::Costunolide, isolated from the stem bark of Magnolia sieboldii, is a sesquiterpene lactone that exhibits various biological and immunological actions. We investigated the induction mechanism of apoptosis by costunolide in a human B cell leukemia NALM-6 cell culture system. Costunolide (10 microM)-induced apoptosis tim...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.31.1024
更新日期:2008-05-01 00:00:00
abstract::We studied in vitro metabolites of 2,4,6,2',4',6'-hexachlorobiphenyl (HCB, IUPAC PCB No. 155) produced by liver microsomes of a phenobarbital (PB)-treated beagle dog. The major metabolites were 3-hydroxy-2,4,6,2',4',6'-HCB (M-1), 4-hydroxy-2,6,2',4',6'-pentachlorobiphenyl (PenCB, M-2) and 3,4-dihydroxy-2,6,2',4',6'-Pe...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.16.852
更新日期:1993-09-01 00:00:00
abstract::Polyethyleneglycol (PEG) compounds have a large hydrogen bonding capability and possess various functions that depend on the length of the chain and conformational diversity. Modification of a drug with PEG is a well-known technology for improving the physicochemical properties and biological responses of a drug. Ther...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章,评审
doi:10.1248/bpb.b13-00087
更新日期:2013-01-01 00:00:00
abstract::The aim of this study was to evaluate the effect of olmesartan (OLME), an angiotensin II receptor antagonist, on an intestinal mucositis model. Briefly, daily intraperitoneal (i.p.) injections of methotrexate (MTX) 7 mg/kg were administered to rats on 3 consecutive days. A subset of these rats was also pretreated with...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b14-00847
更新日期:2015-01-01 00:00:00
abstract::Salt-sensitive hypertension induces renal injury via decreased blood flow in the renal artery (RA), and ion channel dysfunction in RA myocytes (RAMs) may be involved in the higher renal vascular resistance. We examined the effects of several voltage-gated K+ (KV) channel blockers on the resting tension in endothelium-...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b17-00289
更新日期:2017-01-01 00:00:00
abstract::It has been demonstrated that adipose-derived stem cells (ADSCs) secrete cytokines and exhibit diverse pharmacological actions. The present study examined the unknown pharmacological action of ADSCs regarding whitening effects. A conditioned medium of ADSCs (ADSC-CM) was harvested and the whitening effect of ADSC-CM w...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.31.606
更新日期:2008-04-01 00:00:00
abstract::A sulfated galactan (FG) was isolated from the green alga, Codium fragile. Chemical analysis revealed that FG mainly consisted of D-galactose with pyruvic acid (12.3%) and sulfate (11.0%). Methylation and NMR analyses showed that FG was composed of -->3)-beta-D-Galp-(1-->, beta-D-Galp-(1--> and -->3,6)-beta-D-Galp-(1-...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.32.892
更新日期:2009-05-01 00:00:00
abstract::Duloxetine is a widely used antidepressant worldwide. In the present report, we evaluated its capacity to induce micronucleated polychromatic erythrocytes (MNPEs) and micronucleated normochromatic erythrocytes (MNNEs) in mice. Two assays were performed, one with a single chemical administration and the other with dail...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b15-00152
更新日期:2015-01-01 00:00:00
abstract::Mume fruit, the Japanese apricot (Prunus mume SIEB. et ZUCC.), is popular in Japan and is mostly consumed in the pickled form called umeboshi. This fruit is known to have anti-microbial properties, but the principal constituents responsible for the antimicrobial properties have not yet been elucidated. We investigated...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b17-00711
更新日期:2018-01-01 00:00:00
abstract::This study sought to investigate the ameliorating effects of soy 11S protein on the impacts of alcohol consumption in rat hepatocytes and in reducing total cholesterol levels and total lipid levels in the serum. Liver histology and the clinically important enzyme markers (Aspartate Aminotransferase: AST and Alanine Am...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.27.1636
更新日期:2004-10-01 00:00:00
abstract::We previously reported the isolation of a novel cerebroside (1-O-(beta-D-glucopyranosyl)-(2S,3R,4E,8Z)-2-N-palmityloc tadecasphinga-4,8-diene; LCC) from the fruits of Lycium chinense MILL. (Solanaceae) which protected primary cultured rat hepatocytes from the toxicity induced by carbon tetrachloride (CCl4). The presen...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.22.873
更新日期:1999-08-01 00:00:00
abstract::Calprotectin is a calcium- and zinc-binding protein complex that is abundant in cytosol of neutrophils. The concentration of calprotectin in extracellular fluids is greatly increased under various inflammatory conditions in vivo. We recently demonstrated that calprotectin inhibited cell growth and induced apoptosis of...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.22.674
更新日期:1999-07-01 00:00:00
abstract::The in vitro percutaneous permeation of diclofenac from various vehicles was examined using rat abdominal skin as a model membrane. The oleaginous vehicles used in this study consisted of three components: i.e. fatty acid, fatty acid ester and nonpolar oil. The solubilities of sodium diclofenac in formulated vehicles ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.18.571
更新日期:1995-04-01 00:00:00
abstract::The present study was to study the hepatoprotective effects of phloridzin (PHL) on hepatic fibrosis induced by carbon tetrachloride (CCl₄) in rats, on the basis of this investigation, the possible mechanism of PHL was elucidated. Male Sprague Dawley (SD) rats were randomly divided into six groups: control, model, PHL-...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b12-00057
更新日期:2012-01-01 00:00:00
abstract::T cells play a principal role in cellular immunity and govern the regulatory mechanism in humoral immunity. Therefore, T cells play a key role as either effectors or regulators in the immune network. Mizoribine (MZR), an immunosuppressive agent, suppresses both humoral and cellular immunity by acting on both T cells a...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.19.1136
更新日期:1996-09-01 00:00:00
abstract::The present study investigated the effect of 4[(5,6,7,8-tetrahydro-5,5,8,8,-tetramethyl-2-naphthalenyl)carbamoyl] benzoic acid (Am-80), a synthetic retinoid, on spinal cord injury (SCI) in rats. Treatment with Am-80 (orally and subcutaneously) significantly promoted recovery from SCI-induced motor dysfunction. On day ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.32.225
更新日期:2009-02-01 00:00:00