scholarly journals Discovery of Potent and Selective Halogen-Substituted Imidazole-Thiosemicarbazides for Inhibition of Toxoplasma gondii Growth In Vitro via Structure-Based Design

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1618 ◽  
Author(s):  
Agata Paneth ◽  
Lidia Węglińska ◽  
Adrian Bekier ◽  
Edyta Stefaniszyn ◽  
Monika Wujec ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Limiting Factor ◽  
In Vitro Proliferation ◽  
Highly Effective ◽  
Rate Limiting ◽  
Better Than

Employing a simple synthetic protocol, a series of highly effective halogen-substituted imidazole-thiosemicarbazides with anti-Toxoplasma gondii effects against the RH tachyzoites, much better than sulfadiazine, were obtained (IC50s 10.30—113.45 µg/mL vs. ~2721.45 µg/mL). The most potent of them, 12, 13, and 15, blocked the in vitro proliferation of T. gondii more potently than trimethoprim (IC50 12.13 µg/mL), as well. The results of lipophilicity studies collectively suggest that logP would be a rate-limiting factor for the anti-Toxoplasma activity of this class of compounds.

In vivo Nitrate Reductase Activity in Leaves of Pearl Millet, Pennisetum americanum (L.) Leeke

1987 ◽  
Vol 14 (2) ◽  
pp. 125 ◽  
Author(s):  
SV Chanda ◽  
AK Joshi ◽  
PN Krishnan ◽  
YD Singh
Keyword(s):  
Nitrate Reductase ◽  
Reductase Activity ◽  
Potassium Phosphate ◽  
Limiting Factor ◽  
Growth Stages ◽  
In Vivo Assay ◽  
Rate Limiting ◽  
Nr Activity

In the in vivo assay of nitrate reductase (NR) in P. americanum leaves, addition of 1% (v/v) Triton X-100, potassium phosphate buffer (80 mM, pH 7.4) and 1.13 mM NADH to the assay medium resulted in maximum activity. With increasing concentration of NADH, saturation-type kinetics were observed. Based on this data metabolic pool concentration for NADH and apparent Km for nitrate reductase were determined. In field studies with cultivars BJ-104, J-104 and 5141-A of P. americanum, the relative limitation of NO3-, NADH and nitrate reductase in NO3- assimilation was determined. NR activity was measured by four modifications of the in vivo assay technique (with NO3-, with NADH, without NO3- and NADH and with both NO3- and NADH additions to the reaction mixture) and with one in vitro technique. For all the cultivars, NADH was the major rate-limiting factor for in vivo assay during early growth stages, while at later stages, NO3- was limiting. At no stage was NR rate-limiting. It is concluded that NR activity alone may not serve as biochemical marker for improved efficiency of utilisation of nitrogen in P. americanum.

Solubility-Permeability Interplay of Hydrotropic Solubilization Using Response Surface Methodology

2020 ◽  
Vol 10 (3) ◽  
pp. 209-218
Author(s):  
Nidhi Nainwal ◽  
Sunil Jawala ◽  
Ranjit Singh ◽  
Vikas A. Saharan
Keyword(s):  
Sodium Benzoate ◽  
Aqueous Solubility ◽  
Solubility Enhancement ◽  
Limiting Factor ◽  
Apparent Permeability ◽  
Poorly Soluble ◽  
Full Factorial ◽  
Rate Limiting ◽  
Different Levels

Background:: The solubility/dissolution of a drug in the gastrointestinal (GI) region and the permeability of a drug through the GI membrane are the two key parameters governing drug absorption. Poor aqueous solubility is the rate-limiting factor for the absorption of poorly soluble drugs through the GI region. Objective: The purpose of this work is to investigate the influence of two different hydrotropes, namely sodium benzoate (SB), and nicotinamide (NA), at different levels (10-40%) and in combination on the solubility and permeability of poorly soluble drug glibenclamide (GLB). The work will find out, whether the solubility enhancement of glibenclamide using hydrotropes and hydrotropic blends also affects the GI permeability of glibenclamide. Methods: A 32 full factorial design was employed to study the influence of hydrotropic blends of sodium benzoate and nicotinamide on the solubility and permeability of GLB. The solubility and permeability of drugs at different levels (10-40%) of hydrotropes (SB, NA) and their blends are determined using a magnetic stirrer and in vitro Franz diffusion cell, respectively. Results: The results of preliminary studies revealed an increase in the solubility and reduction in the apparent permeability of GLB as a function of increasing levels of both hydrotropes. Conclusion: In this work, it was found that an increase in solubility with hydrotropes results in a decrease in permeability of GLB. The solubility enhancement and the permeability decrease were observed more in hydrotropic blends in comparison to individual hydrotropes. Therefore, it is concluded that both factors, solubility and permeability, must be optimized to achieve appreciable gains in bioavailability.

Regulation of synthesis of oligosaccharyl pyrophosphoryl dolichol during seed germination

1990 ◽  
Vol 68 (3) ◽  
pp. 680-684 ◽  
Author(s):  
Jack W. Rip ◽  
Joyce A. Williams ◽  
Dean C. Crick ◽  
Kenneth K. Carroll
Keyword(s):  
Seed Germination ◽  
Limiting Factor ◽  
Oligosaccharide Synthesis ◽  
Dolichyl Phosphate ◽  
P Content ◽  
Regulation Of Synthesis ◽  
Rate Limiting ◽  
Synthesis Regulation ◽  
Rate Of Accumulation

Subsaturating (approximately physiological) concentrations of [1-14C]dolichol were supplied in vitro to soybean embryo microsomes, to enable the formation of [1-14C]dolichyl phosphate ([1-14C]Dol-P). By including saturating amounts of nonradiolabeled UDP-GlcNAc, GDP-Man, and UDP-Glc individually or in combination in the assay, the extent to which newly formed [1-14C]Dol-P is directed into [1-14C]dolichyl pyrophosphate ([1-14C]Dol-PP) – GlcNAc, [1-14C]Dol-PP-(GlcNAc)2, [1-14C]Dol-P-Man, and [1-14C]Dol-P-Glc could be followed. The addition of UDP-GlcNAc did not appreciably decrease the rate of accumulation of free [1-14C]Dol-P, whereas GDP-Man and UDP-Glc reduced the free [1-14C]Dol-P content of the assays by about 20 and 50%, respectively. The appearance of Dol-P-Man and (or) Dol-P-Glc accounted entirely for the decreased amounts of free Dol-P present. Even in the presence of all three nucleoside diphosphate sugars, about 40–50% of the total [1-14C]Dol-P formed remained in the free phosphate form. The early intermediates Dol-PP-GlcNAc and Dol-PP-(GlcNAc)2 were produced only in trace amounts by microsomes isolated prior to germination and between 2 and 20 h of germination. The availability of Dol-P does not appear to be the rate-limiting factor in Dol-PP-oligosaccharide formation and N-linked glycoprotein formation in this system.Key words: dolichol, dolichyl phosphate, N-oligosaccharide, synthesis regulation.

scholarly journals A robust method for haploid sugar beet in vitro proliferation and hyperhydricity reduction

2017 ◽  
Vol 29 (2) ◽  
pp. 241-250 ◽  
Author(s):  
Arman Pazuki ◽  
Fatemeh Aflaki ◽  
Ekrem Gürel ◽  
Ali Ergül ◽  
Songül Gürel
Keyword(s):  
Sugar Beet ◽  
Plant Growth Regulator ◽  
Effect Sizes ◽  
Coefficient Of Determination ◽  
In Vitro Proliferation ◽  
Dependent Variables ◽  
Effects Of Media ◽  
Hormonal Treatments ◽  
Better Than

AbstractSugar beet is recalcitrant to in vitro tissue culture. Usually, proliferation of in vitro cultured rosette explants is a prerequisite for micropropagation. Although hormonal treatments can induce proliferation in sugar beet rosette explants, they may also result in some side effects. In vitro culture of sugar beet explants and some hormonal treatments make them more prone to hyperhydricity. Effects of media with different concentrations of 6-benzylaminopurine (BAP) and kinetin (Kin) on the proliferation and hyperhydricity of haploid sugar beet explants were investigated. It was observed that 0.2 mg L-1Kin, with a reasonable amount of proliferation and minimum rate of hyperhydricity, performed better than BAP in different concentrations and combinations. The effect sizes of the treatments on the dependent variables were large. The correlation between proliferation and hyperhydricity of the treated explants was statistically negative and the association was large. However, the hormonal treatments without BAP or with the lowest amount of it produced the highest proliferation rate with the least hyperhydricity. The coefficient of determination was R2quadratic = 0.885. The results suggest that, in comparison with BAP, Kin is a potent plant growth regulator for the proliferation of sugar beet haploid explants that causes the least hyperhydricity. Although explants proliferated better in the presence of 0.01 mg L-1BAP in combination with Kin than under Kin alone, the hyperhydricity of the proliferated explants decreased their suitability for in vitro propagation.

Effect of sugar and monoglyceride on fatty acid esterification.

1978 ◽  
Vol 234 (3) ◽  
pp. E236
Author(s):  
Y F Shiau ◽  
W B Long ◽  
J B Weiss
Keyword(s):  
Fatty Acid ◽  
Phosphatidic Acid ◽  
Limiting Factor ◽  
Rat Jejunum ◽  
Acid Pathway ◽  
Mode Of Transport ◽  
Rate Limiting ◽  
Acid Esterification ◽  
Fatty Acid Esterification

The effect of hexose and monoolein on fatty acid esterification was studied in everted rings of rat jejunum. By use of [3H]oleic acid and [U-14C]glucose, esterification via both phosphatidic acid and monoglyceride pathways was quantified. Our results showed that 1) metabolizable sugars stimulate fatty acids esterification regardless of their mode of transport; 2) in the presence of glucose alone, in vitro fatty acid esterification is mediated entirely by the phosphatidic acid pathway; 3) glucose stimulates both esterification pathways in the presence of monoolein; 4) monoolein stimulates only the monoglyceride pathway and has no effect on the phosphatidic acid pathway; and 5) the rate-limiting factor in the presence of monoolein alone is the formation of acyl-CoA, whereas in the presence of glucose alone, the rate-limiting factor is the formation of alpha-glycerophosphate.

scholarly journals Synthesis and In Vitro Anti-Toxoplasma gondii Activity of Novel Thiazolidin-4-one Derivatives

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3029
Author(s):  
Nazar Trotsko ◽  
Adrian Bekier ◽  
Agata Paneth ◽  
Monika Wujec ◽  
Katarzyna Dzitko
Keyword(s):  
Toxoplasma Gondii ◽  
Weight Ratio ◽  
Dimethyl Acetylenedicarboxylate ◽  
Ethyl Bromoacetate ◽  
New Agents ◽  
Inhibition Of Proliferation ◽  
Effective Drugs ◽  
Proliferation In Vitro ◽  
Better Than

Recent findings on the biological activity of thiazolidin-4-ones and taking into account the lack of effective drugs used in the treatment of toxoplasmosis, their numerous side effects, as well as the problem of drug resistance of parasites prompted us to look for new agents. We designed and synthesized a series of new thiazolidin-4-one derivatives through a two-step reaction between 4-substituted thiosemicarbazides with hydroxybenzaldehydes followed by the treatment with ethyl bromoacetate; maleic anhydride and dimethyl acetylenedicarboxylate afforded target compounds. The thiazolidin-4-one derivatives were used to assess the inhibition of Toxoplasma gondii growth in vitro. All active thiazolidine-4-one derivatives (12 compounds) inhibited T. gondii proliferation in vitro much better than used references drugs both sulfadiazine as well as the synergistic effect of sulfadiazine + trimethoprim (weight ratio 5:1). Most active among them derivatives 94 and 95 showed inhibition of proliferation at about 392-fold better than sulfadiazine and 18-fold better than sulfadiazine with trimethoprim. All active compounds (82–88 and 91–95) against T. gondii represent values from 1.75 to 15.86 (CC30/IC50) lower than no cytotoxic value (CC30).

scholarly journals Infection of mouse neural progenitor cells by Toxoplasma gondii affects in vitro proliferation, differentiation and migration

2021 ◽  
Author(s):  
Luiza Bendia Pires ◽  
Helene Santos Barbosa ◽  
Marcelo Felippe Santiago ◽  
Daniel Adesse
Keyword(s):  
Cell Proliferation ◽  
Toxoplasma Gondii ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Congenital Toxoplasmosis ◽  
Neural Progenitor ◽  
In Vitro Proliferation ◽  
Migration Rates ◽  
The Impact

Congenital toxoplasmosis constitutes a major cause of pre- and post-natal complications. Fetal infection with Toxoplasma gondii influences development and can lead to microcephaly, encephalitis, and neurological abnormalities. Few studies have attempted to explain the impact of T. gondii infection on the physiology of mature nerve cells, and no systematic study concerning the effect of infection of neural progenitor cells by T. gondii in the biology of these progenitors is available. We infected cortical intermediate progenitor cell cultivated as neurospheres obtained from E16.5 Swiss Webster mice with T. gondii (Me49 strain) tachyzoites to mimic the developing mouse cerebral cortex in vitro. Infection decreased cell proliferation as detected by Ki67 staining at 48 and 72 hours post infection (hpi) in floating neurospheres, resulting in reduced cellularity at 96 hpi. Neurogenic and gliogenic potential, assessed in plated neurospheres, was shown to be impaired in infected cultures, as indicated by neurofilament heavy chain (NF-200) and GFAP staining, respectively. To further investigate the impact of infection on neuronal differentiation, Neuro2a neuroblasts were infected and after 24 hpi, neurogenic differentiation was induced with serum withdrawal. We confirmed that infection induces a decrease in neuroblast-neuron differentiation rates in cells stained for NF-200, with reduced neuritogenesis. Migration rates were analyzed in plated neurospheres. At 120 h after plating, infected cultures exhibited decreased overall migration rates and altered the radial migration of nestin-, GFAP- and NF-200-positive cells. These findings indicate that T. gondii infection of neural progenitor cells may lead to reduced neuro/gliogenesis due to an imbalance in cell proliferation alongside an altered migratory profile. If translated to the in vivo situation, these data could explain, in part, the cortical malformations observed in congenitally infected individuals.

Cytological changes induced by platinum-thymine in sarcoma-180 cells: Electron microscopy study

1990 ◽  
Vol 48 (3) ◽  
pp. 290-291
Author(s):  
Gustav Ofosu
Keyword(s):  
Mammalian Cells ◽  
Antitumor Agent ◽  
Microscopy Study ◽  
Electron Microscopy Study ◽  
Limiting Factor ◽  
Sarcoma 180 ◽  
Electron Microscopic ◽  
Cytological Changes

Platinum-thymine has been found to be a potent antitumor agent, which is quite soluble in water, and lack nephrotoxicity as the dose-limiting factor. The drug has been shown to interact with DNA and inhibits DNA, RNA and protein synthesis in mammalian cells in vitro. This investigation was undertaken to elucidate the cytotoxic effects of piatinum-thymine on sarcoma-180 cells in vitro ultrastructurally, Sarcoma-180 tumor bearing mice were treated with intraperitoneal injection of platinum-thymine 40mg/kg. A concentration of 60μg/ml dose of platinum-thymine was used in in vitro experiments. Treatments were at varying time intervals of 3, 7 and 21 days for in vivo experiments, and 30, 60 and 120 min., 6, 12, and 24th in vitro. Controls were not treated with platinum-thymine.Electron microscopic analyses of the treated cells in vivo and in vitro showed drastic cytotoxic effect.

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