scholarly journals Antifungal Activities of 4″,6″-Disubstituted Amphiphilic Kanamycins

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1882 ◽  
Author(s):  
Madher N. Alfindee ◽  
Yagya P. Subedi ◽  
Michelle M. Grilley ◽  
Jon Y. Takemoto ◽  
Cheng-Wei T. Chang
Keyword(s):  
Minimal Growth ◽  
Intact Cells ◽  
Antifungal Activities ◽  
First Order ◽  
Fluorogenic Dyes ◽  
Growth Inhibitory ◽  
Cellular Reactive Oxygen Species ◽  
Plasma Membrane Permeabilization ◽  
Dye Fluorescence ◽  
High Concentrations

Amphiphilic kanamycins derived from the classic antibiotic kanamycin have attracted interest due to their novel bioactivities beyond inhibition of bacteria. In this study, the recently described 4″,6″-diaryl amphiphilic kanamycins reported as inhibitors of connexin were examined for their antifungal activities. Nearly all 4″,6″-diaryl amphiphilic kanamycins tested had antifungal activities comparable to those of 4″,6″-dialkyl amphiphilic kanamycins, reported previously against several fungal strains. The minimal growth inhibitory concentrations (MICs) correlated with the degree of amphiphilicity (cLogD) of the di-substituted amphiphilic kanamycins. Using the fluorogenic dyes, SYTOXTM Green and propidium iodide, the most active compounds at the corresponding MICs or at 2×MICs caused biphasic dye fluorescence increases over time with intact cells. Further lowering the concentrations to half MICs caused first-order dye fluorescence increases. Interestingly, 4×MIC or 8×MIC levels resulted in fluorescence suppression that did not correlate with the MIC and plasma membrane permeabilization. The results show that 4″,6″-diaryl amphiphilic kanamycins are antifungal and that amphiphilicity parameter cLogD is useful for the design of the most membrane-active versions. A cautionary limitation of fluorescence suppression was revealed when using fluorogenic dyes to measure cell-permeation mechanisms with these antifungals at high concentrations. Finally, 4″,6″-diaryl amphiphilic kanamycins elevate the production of cellular reactive oxygen species as other reported amphiphilic kanamycins.

scholarly journals Akinetic model for the consumption of stabilizer in single base gun propellants

2002 ◽  
Vol 67 (2) ◽  
pp. 103-109 ◽  
Author(s):  
Ljiljana Jelisavac ◽  
Milos Filipovic
Keyword(s):  
Life Time ◽  
Order Reaction ◽  
Zero Order ◽  
Final Phase ◽  
Single Base ◽  
First Order ◽  
Low Concentrations ◽  
Zero Order Reaction ◽  
High Concentrations ◽  
Gun Propellants

A suitable kinetic model for the consumption of stabilizer (diphenylamine) in single base gun propellants was investigated and successfully verified. The model assumes that a reaction of shifting order can be applied for the consumption of diphenylamine in single base gun propellants. It was found that the experimental data were well evaluated by a first-order reaction at high concentrations of diphenylamine in the propellant, but by a zero-order reaction at low concentrations during the final phase of the propellant life time. The mechanism of diphenylamine depletion was discussed with relation to the model and the ageing behavior of the propellants. The kinetic parameters of this model, which permit the calculation of the time up to complete consumption of the diphenylamine, were determined. The results were compared with the kinetic data obtained by a widely accepted model, which combines formally reactions of first and zero order, designated as an "exponential and linear" model. All comparisons gave satisfactory agreement.

scholarly journals Syncatalytic inactivation of prolyl 4-hydroxylase by anthracyclines

1988 ◽  
Vol 251 (2) ◽  
pp. 365-372 ◽  
Author(s):  
V Günzler ◽  
H M Hanauske-Abel ◽  
R Myllylä ◽  
D D Kaska ◽  
A Hanauske ◽  
...  
Keyword(s):  
Reaction Rate ◽  
Total Radioactivity ◽  
Human Origin ◽  
Iron Ion ◽  
First Order ◽  
Irreversible Inhibitors ◽  
Semiquinone Radicals ◽  
Enzyme Subunits ◽  
High Concentrations ◽  
Reaction Cycles

The anthracyclines doxorubicin and daunorubicin were found to act as irreversible inhibitors of prolyl 4-hydroxylase. The reaction rate for enzyme from both chick and human origin was first order, the concentration of inhibitor giving 50% inhibition being 60 microM for both compounds after 1 h. The effect was dependent on the presence of iron ions in the reaction mixture. Inactivation could be prevented by addition of high concentrations of ascorbate, but not 2-oxoglutarate, before the inactivation period. The same results were obtained with competitive analogues of these cosubstrates. Lysyl hydroxylase from chick embryos was also susceptible to inactivation. Its activity was decreased by 50% after incubation for 1 h with a 150 microM concentration of the inhibitors. When chick-embryo prolyl 4-hydroxylase was incubated with [14-14C]doxorubicin, both enzyme subunits were radioactively labelled, about 70% of the total radioactivity being found in the alpha-subunit. Since the anthracyclines are known to undergo a redox reaction generating semiquinone radicals with Fe3+ only, the results suggest that the enzyme-bound iron ion is oxidized to a tervalent intermediate in uncoupled reaction cycles. The data also suggest that both enzyme subunits contribute to the catalytic site of prolyl 4-hydroxylase.

Inhibition of initiation of protein synthesis by tosyl-L-lysyl chloromethyl ketone

1981 ◽  
Vol 59 (5) ◽  
pp. 321-327 ◽  
Author(s):  
Majambu Mbikay ◽  
Michael D. Garrick
Keyword(s):  
Protein Synthesis ◽  
Initiation Complex ◽  
Intact Cells ◽  
Chloromethyl Ketone ◽  
Chain Initiation ◽  
High Concentrations

Tosyl-L-lysyl chloromethyl ketone (TLCK) inhibits protein synthesis in intact cells and lysates. Its presence leads to polyribosome disaggregation. This inhibition is probably at the level of chain initiation because it does not slow poly(U)-dependent elongation of poly(F). This drug activates an inhibitor similar to the heme-controlled repressor in the postribosomal supernatant. High concentrations of ATP and GTP affect inhibitions of translation by the heme-controlled repressor and TLCK in a similar fashion. The latter also interferes with formation of the 40S initiation complex. Its action on translation can be prevented by preliminary incubation with thiols.

scholarly journals Fusion accessibility of endocytic compartments along the recycling and lysosomal endocytic pathways in intact cells.

1989 ◽  
Vol 109 (5) ◽  
pp. 2097-2104 ◽  
Author(s):  
N H Salzman ◽  
F R Maxfield
Keyword(s):  
Time Course ◽  
Late Endosome ◽  
Intact Cells ◽  
Degradative Pathway ◽  
First Order ◽  
First Order Kinetics ◽  
Recycling Pathway ◽  
Endocytic Vesicles ◽  
Endocytic Compartments ◽  
Endocytic Pathways

A fluorescence assay developed for the quantitation of intracellular fusion of sequentially formed endocytic compartments (Salzman, N. H., and F. R. Maxfield. 1988 J. Cell Biol. 106:1083-1091) has been used to measure the time course of endosome fusion accessibility along the recycling and degradative endocytic pathways. Transferrin (Tf) was used to label the recycling pathway, and alpha2-macroglobulin (alpha 2 M) was used to label the lysosomal degradative pathway. Along the degradative pathway, accessibility of vesicles containing alpha 2M to fusion with subsequently formed endocytic vesicles decreased with apparent first order kinetics. The t12 for the loss of fusion accessibility was approximately 8 min. The behavior of Tf is more complex. Initially the fusion accessibility of Tf decayed rapidly (t1/2 less than 3 min), but a constant level of fusion accessibility was then observed for 10 min. This suggests that Tf moves through one fusion accessible endosome rapidly and then enters a second fusion accessible compartment on the recycling pathway. At 18 degrees C, fusion of antifluorescein antibodies (AFA) containing vesicles with F-alpha 2M was observed when the interval between additions was 10 min. However, if the interval was increased to 1 h, no fusion with incoming vesicles was observed. These results identify the site of F-alpha 2M accumulation at 18 degrees C as a prelysosomal late endosome that no longer fuses with newly formed endosomes since no delivery to lysosomes is observed at this temperature.

Studies on the Mechanism of Copper Toxicity inChlorella

Weed Science ◽  
1974 ◽  
Vol 22 (5) ◽  
pp. 443-449 ◽  
Author(s):  
Arturo Cedeno-Maldonado ◽  
J. A. Swader
Keyword(s):  
Electron Transport ◽  
Photosynthetic Apparatus ◽  
Copper Toxicity ◽  
Photosynthetic Electron Transport ◽  
Autotrophic Growth ◽  
Intact Cells ◽  
Cupric Ion ◽  
High Concentrations ◽  
Short Time ◽  
Photosynthesis And Respiration

Autotrophic growth, photosynthesis, and respiration ofChlorella sorokinianaShihira and Krauss were inhibited by the cupric ion, but photosynthesis was more sensitive than respiration. The percent inhibition was determined by the ratio of cells to cupric ions present. Photosynthesis and respiration were inhibited within 2 and 5 min, respectively, after adding 1.0 mM cupric ions.Chlorellacells which had been incubated for a short time in concentrations of the cupric ion that completely inhibited photosynthesis were not able to grow when cultured in a fresh medium without cupric ions, indicating high concentrations of the ion may have destroyed the photosynthetic apparatus and deprived the cells of their ability for autotrophic growth. Dark preincubation of the cells, as well as high bicarbonate concentrations in the assay medium, decreased inhibition. Treatment with cupric ions reduced the cellular chlorophyll and sulfhydryl content, but anaerobiosis, a condition that increased toxicity, had little effect on the sulfhydryl content. Electron transport in photosystems I and II in intactChlorellacells was inhibited, but the specific sites of inhibition in the photosynthetic electron transport chain could not be determined using intact cells.

Effects of protamine and strophanthin on mitochondrial potassium, sodium and water

1960 ◽  
Vol 199 (4) ◽  
pp. 653-656
Author(s):  
Leonard Share
Keyword(s):  
Rat Liver ◽  
Sodium Concentration ◽  
Water Metabolism ◽  
Intact Cells ◽  
Kidney Mitochondria ◽  
Potassium Sodium ◽  
Isolated Mitochondria ◽  
Liver And Kidney ◽  
Uncoupling Of Oxidative Phosphorylation ◽  
High Concentrations

A study was made of the effects of certain agents, which inhibit potassium transport in intact cells, on the potassium, sodium and water metabolism of isolated mitochondria. Protamine (4 mg/100 ml) induced swelling in rat liver and kidney mitochondria and impaired the ability of these mitochondria to concentrate potassium. These actions appeared to be associated with the uncoupling of oxidative phosphorylation. Protamine was without effect on the mitochondrial sodium concentration. Strophanthin at extremely high concentrations (1 gm/100 ml) was also found to induce swelling of rat liver, kidney and heart mitochondria and to interfere with the ability of the mitochondria to concentrate potassium. There was a tendency for mitochondrial sodium concentration to be elevated. It is concluded that the actions of protamine and strophanthin on mitochondria are qualitatively and quantitatively different from the actions of these substances on intact cells and that there are basic differences between the potassium concentrating mechanisms in mitochondria and in intact cells.

scholarly journals The Kinetics of Clearance from the Circulation of Man of Heparin and a Semi-Synthetic Heparin Analogue

1977 ◽  
Author(s):  
D. A. Lane ◽  
R. Michalski ◽  
V. V. Kakkar
Keyword(s):  
High Specificity ◽  
Antithrombotic Agent ◽  
First Order ◽  
First Order Kinetics ◽  
Zero Order Kinetics ◽  
Low Concentrations ◽  
Equal Dose ◽  
Rapid Clearance ◽  
The Difference ◽  
High Concentrations

A study has been made of a low molecular weight semi-synthetic heparin analogue, (SSHA) that may be clinically useful as an antithrombotic agent because of itsreported high specificity for potentiating antithrombin III activity. The clearance from the circulation of both heparin and the analogue has been studied in man following intravenous injection. Heparin obeyed almost zero order kinetics when assayed using a specific anti-Xa assay and first order kinetics when measured with KCCT. At high concentrations the heparin analogue was cleared with first order kinetics when assayed both with the anti-Xa assay and with KCCT. At low concentrations the analogue produced between one half and two-thirds of the anti-Xa activity of an equal dose of heparin, producing only a small prolongation of KCCT. With increasing dose, the more specific anti-Xa potentiating effect of SSHA decreased in part because of the difference in kinetic behaviour between heparin and SSHAbut largely because of a flattening of its anti-Xa dose response curve. Because of the initial more rapid clearance of higher doses of heparin from plasma when it is measured by the KCCT, these results suggest that the use of KCCT can cause a small underestimate of circulating heparin anti-thrombotic activity.

scholarly journals Investigation of the Kinetic Regularities of the Process of Biodegradation of Betaine Surfactant by Bacteria of the Genus Pseudomonas

2021 ◽  
Vol 11 (19) ◽  
pp. 8939
Author(s):  
Anastasia S. Burlachenko ◽  
Olesya V. Salishcheva ◽  
Lyubov S. Dyshlyuk ◽  
Alexander Y. Prosekov
Keyword(s):  
Kinetic Data ◽  
Industrial Wastewater ◽  
Surfactant Concentration ◽  
Time Interval ◽  
Organic Substances ◽  
High Concentration ◽  
First Order ◽  
High Concentrations ◽  
Biological Decomposition ◽  
Toxic Organic Substances

Surfactants are extremely common organic compounds that enter the environment in large quantities in the form of household and industrial wastewater. The toxicity of surfactants for biological systems, the high concentration of substances and the duration of the bioremediation process of polluted ecosystems requires improving the biotechnology of microbial wastewater treatment for surfactants. The purpose of this work is to study the kinetic laws of the reaction of the biological decomposition of betaine surfactants. Pseudomonas bacteria were used as bio-destructors of the surfactants. Kinetic data were obtained to create the possibility of further optimization of research on the biodegradation of toxic organic substances. The strains that were promising destructors of cocamidopropylbetaine were selected. The toxicity of high concentrations of surfactants in relation to microorganisms of the genus Pseudomonas was proven. Safe values of the surfactant concentration for conducting biodegradation tests were found. A kinetic model of the biodestructive process was constructed. It proves that the processes of biodegradation are described by a kinetic equation of the first order. With the derived equation, it is possible to determine the time interval of biodegradation of cocamidopropylbetaine to the specified values by means of mathematical calculations.

scholarly journals 858 PB 437 EVALUATION OF DIKEGULAC-SODIUM AND MEFLUIDIDE FOR GROWTH CONTROL OF ASIATIC AND CONFEDERATE JASMINE

HortScience ◽  
1994 ◽  
Vol 29 (5) ◽  
pp. 556d-556
Author(s):  
Jeffrey G. Norcini ◽  
James H. Aldrich
Keyword(s):  
Plant Growth ◽  
Growth Control ◽  
Inhibitory Effect ◽  
Lateral Growth ◽  
Single Application ◽  
Growth Inhibitory Effect ◽  
Minimal Growth ◽  
Optimum Treatment ◽  
Woody Vine ◽  
Growth Inhibitory

The effectiveness of three concentrations of either dikegulac-sodium or mefluidide on the growth of two containerized woody vine crops was investigated. A single application of dikegulac-sodium at 1600, 3200, or 4800 mg·liter-1 or mefluidide at 600, 1200, or 1800 mg·liter-1 was applied to either 3.8-liter containers of Asiatic jasmine (Trachelosoerum asiacticum Siebold and Zucc.) or staked confederate jasmine (Trachelosperum jasminiodes (Lindl.) Lem.) on 25 May 1993. Two additional applications were made at 8 week intervals after transplanting to 9.5-liter containers. Plant growth and phytotoxicity were evaluated 0, 4, and 8, and 1, 2, 4, and 8 weeks after application, respectively. Dikegulac-sodium at 3200 mg·liter-1 was the optimum treatment for suppressing the lateral growth of Asiatic jasmine and the vertical growth of confederate jasmine with minimal phytotoxicity. Dikegulac-sodium at 4800 mg·liter-1 excessively inhibited growth of both species and resulted in unacceptable phytotoxicity. All mafluidide treatments had minimal growth inhibitory effect on either species.

scholarly journals Cytotoxic Effects of Coated Gold Nanoparticles on PC12 Cancer Cell

2018 ◽  
Vol 7 ◽  
pp. e1110
Author(s):  
Hadi Zare Marzouni ◽  
Fazel Tarkhan ◽  
Amir Aidun ◽  
Kiana Shahzamani ◽  
Hamid Reza Jahan Tigh ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Amino Acid ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Oxygen Species ◽  
Cytotoxic Effects ◽  
Coated Nanoparticles ◽  
Cellular Life ◽  
Cellular Reactive Oxygen Species ◽  
High Concentrations

Background: The use of gold nanoparticles in medicine and especially in cancer treatment has been of interest to researchers. The effectiveness of this nanoparticle on cells significantly depends on the amount of its entry into the cells. This study was performed to compare the rate and mechanism of effect of gold nanoparticles coated with different amino acid on PC12 cancer cell line.Materials and Methods: The PC12 cells line were exposed to various concentrations of amino acid coated and uncoated gold nanoparticles (0.5, 2.5 and 5 μM). Cell death rate was determined according to level of Lactate dehydrogenase (LDH) release from cells and MTT assay. In addition cell morphology and the amount of Cellular Reactive oxygen species (ROS) were studied.Results: The uncoated gold nanoparticles have shown minor effects on cellular life. Gold nanoparticles coated by tryptophan at high concentrations (2.5, 5 and 25μM) increase in cancer cells metabolic activity. Gold nanoparticles coated by Aspartate also produce the largest amount of LDH and ROS in cancer cells and therefore caused of highest rate of apoptosis.Conclusion: The results showed that the nanoparticles coated with amino acids are affected on cellular metabolism and apoptosis more than uncoated nanoparticles. Also the smallest coated nanoparticles (coated by aspartate) have the most influence and by increasing the size, this effect was reduced. [GMJ.2018;7:e1110]

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