In vitro susceptibilities of clinical yeast isolates to the new antifungal eberconazole compared with their susceptibilities to clotrimazole and ketoconazole. (1/66)

The antifungal activity of eberconazole, a new imidazole derivative, against 124 clinical isolates of Candida comprising eight different species and to 34 isolates of Cryptococcus neoformans was compared to those of clotrimazole and ketoconazole. MICs of eberconazole, determined by the National Committee for Clinical Laboratory Standards standardized microbroth method, were equal to or lower than those of other azoles, especially for Candida krusei and Candida glabrata, which are usually resistant to triazoles.  (+info)

Induction of apoptosis in leukemic cells by the reversible microtubule-disrupting agent 2-methoxy-5-(2',3',4'-trimethoxyphenyl)-2,4,6-cycloheptatrien-1 -one: protection by Bcl-2 and Bcl-X(L) and cell cycle arrest. (2/66)

We have found that the bicyclic colchicine analogue 2-methoxy-5-(2',3',4'-trimethoxyphenyl)-2,4,6-cycloheptatrien-1-on e (MTC) induced a dose- and time-dependent apoptotic response in human leukemic cells. MTC and colchicine rapidly disrupted the microtubule integrity and arrested cells at the G2-M phase before the onset of apoptosis. These responses were mediated by microtubule inhibition because 2-methoxy-5-[[3-(3,4,5-trimethoxyphenyl)propionyl]amino]-2,4,6-cycloh eptatrien-1-one and lumicolchicine, inactive analogues of MTC and colchicine, respectively, were unable to promote microtubule disassembly, cell cycle arrest, and apoptosis. Although 1 microM MTC induced a complete microtubule disruption after 1 h of incubation in human leukemic HL-60 cells that led to an accumulation of cells at the G2-M phase, MTC-induced apoptosis occurred after 9 h of treatment. This indicates the existence of a rather long lag between microtubule disruption and the onset of apoptosis. Unlike colchicine, the removal of MTC during this lag resulted in rapid microtubule repolymerization, followed by restoration of normal cell cycle and cell growth. MTC, but not 2-methoxy-5-[[3-(3,4,5-trimethoxyphenyl)-propionyl]amino]-2,4,6-cyclo heptatrien-1-one, induced c-jun expression as well as c-Jun NH2-terminal kinase and caspase activation, indicating that these signaling pathways are triggered by the specific action of MTC on microtubules. Caspase inhibition prevented MTC-induced apoptosis. Overexpression of bcl-2 or bcl-xL by gene transfer in human erythroleukemic HEL cells abrogated MTC-induced apoptosis, but cells remained arrested in G2-M, suggesting that bcl-2 and bcl-xL block the signaling pathway between G2-M arrest and triggering of apoptosis. MTC-treated bcl-2 and bcl-xL-transfected HEL cells recovered their capacity to proliferate after MTC removal. These results indicate that microtubule inhibition induces G2-M arrest and apoptosis in leukemic cells, showing a lag phase between G2-M arrest and the onset of apoptosis, regulated by bcl-2 and bcl-xL, during which MTC displays a reversible action on microtubule depolymerization and G2-M cell cycle arrest. Thus, MTC is a potent apoptotic inducer on human leukemic cells and shows a remarkable reversible action on microtubule network and cell cycle before commitment for apoptosis is reached.  (+info)

Cytotoxicity of the hinokitiol-related compounds, gamma-thujaplicin and beta-dolabrin. (3/66)

Gamma-thujaplicin and beta-dolabrin, the constituents of the wood of Thujopsis dolabrata Sieb. et Zucc. var. hondai showed strong in vitro cytotoxic effects against the human stomach cancer cell lines KATO-III and Ehrlich's ascites carcinoma. The cytotoxic effects of the two compounds against both tumor cell lines were clear when cell growth was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Gamma-thujaplicin and beta-dolabrin at 0.32 microg/ml inhibited cell growth of human stomach cancer KATO-III by 85 and 67%, and Ehrlich's ascites carcinoma by 91 and 75%, respectively. There is no large difference in cytotoxicity between these compounds, but the activity of gamma-thujaplicin was slightly more potent than that of beta-dolabrin. On the other hand, hinokitiol acetate did not show a cytotoxic effect, suggesting that at least a part of the mechanism of the cytotoxic effect of hinokitiol-related compounds is due to metal chelation between the carbonyl group at C-1 and the hydroxyl group at C-2 in the tropolone skeleton of these molecules. The acute toxicities [50% lethal dose (LD50) value: intraperitoneal injection, Van der Waedem] of gamma-thujaplicin and beta-dolabrin in mice were 277 mg/kg and 232 mg/kg, respectively.  (+info)

Influence of plant terpenoids on the permeability of mitochondria and lipid bilayers. (4/66)

Five sesquiterpene alcohol esters of the carotane series, from plants of the genus Ferula, were investigated with regard to their capacity to modify the ion permeability of both planar lipid bilayers and mitochondria. These compounds are subdivided into two structural groups that differ in their effects on membrane permeability. Complex esters of sesquiterpene alcohols with aliphatic acids, which constituted the first group (lapidin and lapiferin), do not possess ionophoric properties. The second group comprised complex esters of sesquiterpene alcohols with aromatic acids (ferutinin, tenuferidin and ferutidin), all of which increase cation permeability of lipid bilayers and mitochondria in a dose-dependent manner. A pronounced selectivity of the terpenoid-modified membranes for divalent cations versus monovalent cations was found. Evidence of a carrier mechanism for terpenoid-induced ion transport is demonstrated. A tentative complex composed of a divalent cation with two molecules of membrane-active terpenoid is proposed.  (+info)

Antibacterial activity of tropolone. (5/66)

Tropolone was shown to be bacteriostatic and bactericidal for a wide range of bacterial species. This antibacterial activity was quantitated using standard methods. Tropolone treatment of whole cells resulted in cell lysis characterized by bleb formation and subsequent loss of cell contents after rupture of the bleb. Although bleb formation and lysis did not occur in the presence of 20% sucrose, cell viability was lost. Spheroplasts and protoplasts also lysed in the presence of tropolone. These results indicate that tropolone acts on the cell wall or envelope and on the plasma membrane.  (+info)

Studies on the subsite structure of amylases. I. Interaction of glucoamylase with substrate and analogues studied by difference-spectrophotometry. (6/66)

Studies were made on the ultraviolet difference-spectra of glucoamylase from Rhizopus niveus [EC 3.2.1.3] specifically produced by the substrate maltose and the inhibitors, glucose, glucono-1: 5-lactone (gluconolactone), methyl beta-D-glucoside, cellubiose, and cyclohexa-, and cyclohepta-amyloses. Of these, maltose and gluconolactone produced characteristic difference spectra with a trough near 300 nm. Based on studies with a model compound for a tryptophan residue, Ac-Trp, this trough was attributed to the effect of a negative charge upon the tryptophan residue. From the concentration dependency of the difference spectra, the dissociation constants of the complexes between the enzyme and maltose, glucose, and gluconolactone were evaluated to be 1.2 mM, 51 mM, and 1.5 mM, respectively. These values are in good agreement with the values of Km or K1 obtained from the steady-state kinetics. The difference-spectrophotometric data suggested that referring to the values of subsite affinities of glucoamylase, maltose, and gluconolactone occupy mainly Subsite 1, where the non-reducing-end glucose residue of a substrate is bound in a productive form and that a tryptophan residue with shows a trough near 300 nm in difference spectra is located in this subsite.  (+info)

Antibacterial activity of tropilidine and tropone. (7/66)

The seven-membered ring compounds tropilidine and tropone were shown to be bacteriostatic and bactericidal for a wide range of bacterial species.  (+info)

Alicyclobacillus herbarius sp. nov., a novel bacterium containing omega-cycloheptane fatty acids, isolated from herbal tea. (8/66)

A thermo-acidophilic gram-positive bacterium, strain CP-1T, which grows aerobically at 35-65 degrees C (optimum 55-60 degrees C) and at pH 3.5-6.0 (optimum pH 4.5-5.0), was isolated from a herbal tea made from the dried flowers of hibiscus. Phylogenetic analysis of the 16S rRNA gene sequences showed that this bacterium was clearly distinguishable from previously described species of the genera Alicyclobacillus and Sulfobacillus. Strain CP-1T had unique omega-cycloheptane fatty acids as the major membrane lipid component, a characteristic which is peculiar to Alicyclobacillus cycloheptanicus. However, phenotypic and chemotaxonomic characteristics of strain CP-1T were different from those of the type strain of A. cycloheptanicus. DNA-DNA hybridization between the type strains of Alicyclobacillus species and Sulfobacillus disulfidooxidans was <20%, indicating that strain CP-1T represents a distinct species. On the basis of these results, the name Alicyclobacillus herbarius is proposed for this organism. The type strain is strain CP-1T (= DSM 13609T = IAM 14883T = NRIC 0477T).  (+info)

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