scholarly journals In Vitro Inhibition of Toxoplasma gondii by Four New Derivatives of Artemisinin

2006 ◽  
Vol 50 (12) ◽  
pp. 4206-4208 ◽  
Author(s):  
Lorraine Jones-Brando ◽  
John D'Angelo ◽  
Gary H. Posner ◽  
Robert Yolken
Keyword(s):  
Cell Culture ◽  
Side Effects ◽  
Toxoplasma Gondii ◽  
In Vitro Inhibition ◽  
Derivatives Of

ABSTRACT Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is medically important and distributed worldwide. Currently available medications are limited in terms of efficacy and side effects. We synthesized novel, nonacetal, hydrolytically stable derivatives of artemisinin and showed that they inhibit the replication of Toxoplasma gondii in cell culture.

scholarly journals Artemisone and Artemiside Control Acute and Reactivated Toxoplasmosis in a Murine Model

2009 ◽  
Vol 53 (10) ◽  
pp. 4450-4456 ◽  
Author(s):  
Ildiko R. Dunay ◽  
Wing Chi Chan ◽  
Richard K. Haynes ◽  
L. David Sibley
Keyword(s):  
Side Effects ◽  
Toxoplasma Gondii ◽  
Murine Model ◽  
Acute Infection ◽  
Immunocompromised Patients ◽  
Artemisinin Derivatives ◽  
Parasite Replication ◽  
Derivatives Of

ABSTRACT Immunocompromised patients are at risk of developing toxoplasmosis, and although chemotherapy is available, standard treatments are often complicated by severe side effects. Artemisinin is a new highly potent antimalarial drug that has activity against Toxoplasma gondii in vitro. However, artemisinin derivatives have previously been ineffective in vivo using a rat model of toxoplasmosis. In the present study, the efficacy of several new artemisinin derivates was investigated for treatment of mice infected with the parasite Toxoplasma gondii. Artemiside and artemisone displayed better inhibition than either artemisinin or artesunate against the parasite in vitro. Artemiside and artemisone treatment controlled parasite replication in vivo, and mice survived the acute infection. In a murine model of reactivated toxoplasmosis, both drugs increased survival, although artemiside was more effective. These results indicate that these newer derivatives of artemisinin may have potential for treatment of toxoplasmosis.

In vitro inhibition of Toxoplasma gondii by the anti-malarial candidate, 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol

2016 ◽  
Vol 65 (5) ◽  
pp. 494-499 ◽  
Author(s):  
Chun-Feng Xin ◽  
Hye-Sook Kim ◽  
Akira Sato ◽  
Hak-Jae Lee ◽  
You-Won Lee ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
In Vitro Inhibition

Inhibitors of Acetylcholinesterase Derived from 7-Methoxytacrine and Their Effects on the Choline Transporter CHT1

2016 ◽  
Vol 43 (1-2) ◽  
pp. 45-58 ◽  
Author(s):  
Zdenka Kristofikova ◽  
Jan Ricny ◽  
Ondrej Soukup ◽  
Jan Korabecny ◽  
Eugenie Nepovimova ◽  
...  
Keyword(s):  
Side Effects ◽  
Amyloid Β ◽  
Acetylcholinesterase Inhibitors ◽  
Side Chain ◽  
Choline Transporter ◽  
Disease Therapy ◽  
Cortical Membranes ◽  
Derivatives Of

Background: Reversible acetylcholinesterase inhibitors are used in Alzheimer disease therapy. However, tacrine and its derivatives have severe side effects. Derivatives of the tacrine analogue 7-methoxytacrine (MEOTA) are less toxic. Methods: We evaluated new derivatives of 7-MEOTA (2 homodimers linked by 2 C4-C5 chains and 5 N-alkylated C4-C8 side chain derivatives) in vitro, using the rat hippocampal choline transporter CHT1. Results: Some derivatives were effective inhibitors of rat acetylcholinesterase and comparable with 7-MEOTA. All derivatives were able to inhibit CHT1, probably via quaternary ammonium, and this interaction could be involved in the enhancement of their detrimental side effects and/or in the attenuation of their promising effects. Under conditions of disrupted lipid rafts, the unfavorable effects of some derivatives were weakened. Only tacrine was probably able to stereospecifically interact with the naturally occurring amyloid-β isoform and to simultaneously stimulate CHT1. Some derivatives, when coincubated with amyloid β, did not influence CHT1. All derivatives also increased the fluidity of the cortical membranes. Conclusion: The N-alkylated derivative of 7-MEOTA bearing from C4 side chains appears to be the most promising compound and should be evaluated in future in vivo research.

scholarly journals Determination of lumefantrine as an effective drug against Toxoplasma gondii infection – in vitro and in vivo study

Parasitology ◽  
2020 ◽  
pp. 1-7
Author(s):  
Dawei Wang ◽  
Mengen Xing ◽  
Saeed El-Ashram ◽  
Yingying Ding ◽  
Xiao Zhang ◽  
...  
Keyword(s):  
Side Effects ◽  
Toxoplasma Gondii ◽  
Parasite Burden ◽  
Vero Cells ◽  
Negative Control ◽  
Protective Mechanism ◽  
High Dose ◽  
Mouse Tissues

Abstract Toxoplasma gondii is an obligate intracellular protozoan parasite, which can infect almost all warm-blooded animals, including humans, leading to toxoplasmosis. Currently, the effective treatment for human toxoplasmosis is the combination of sulphadiazine and pyrimethamine. However, both drugs have serious side-effects and toxicity in the host. Therefore, there is an urgent need for the discovery of new anti-T. gondii drugs with high potency and less or no side-effects. Our findings suggest that lumefantrine exerts activity against T. gondii by inhibiting its proliferation in Vero cells in vitro without being toxic to Vero cells (P ≤ 0.01). Lumefantrine prolonged mice infected with T. gondii from death for 3 days at the concentration of 50 μg L−1 than negative control (phosphate-buffered saline treated only), and reduced the parasite burden in mouse tissues in vivo (P ≤ 0.01; P ≤ 0.05). In addition, a significant increase in interferon gamma (IFN-γ) production was observed in high-dose lumefantrine-treated mice (P ≤ 0.01), whereas interleukin 10 (IL-10) and IL-4 levels increased in low-dose lumefantrine-treated mice (P ≤ 0.01). The results demonstrated that lumefantrine may be a promising agent to treat toxoplasmosis, and more experiments on the protective mechanism of lumefantrine should be undertaken in further studies.

scholarly journals Determining UV Inactivation of Toxoplasma gondii Oocysts by Using Cell Culture and a Mouse Bioassay

2010 ◽  
Vol 76 (15) ◽  
pp. 5140-5147 ◽  
Author(s):  
Michael W. Ware ◽  
Swinburne A. J. Augustine ◽  
David O. Erisman ◽  
Mary Jean See ◽  
Larry Wymer ◽  
...  
Keyword(s):  
Cell Culture ◽  
Toxoplasma Gondii ◽  
Real Time Pcr ◽  
Scid Mouse ◽  
Low Pressure ◽  
Water Disinfection ◽  
Uv Exposure ◽  
Mouse Bioassay ◽  
Promising Alternative

ABSTRACT The effect of UV exposure on Toxoplasma gondii oocysts has not been completely defined for use in water disinfection. This study evaluated UV-irradiated oocysts by three assays: a SCID mouse bioassay, an in vitro T. gondii oocyst plaque (TOP) assay, and a quantitative reverse transcriptase real-time PCR (RT-qPCR) assay. The results from the animal bioassay show that 1- and 3-log10 inactivation is achieved with 4 mJ/cm2 UV and 10 mJ/cm2 low-pressure UV, respectively. TOP assay results, but not RT-qPCR results, correlate well with bioassay results. In conclusion, a 3-log10 inactivation of T. gondii oocysts is achieved by 10-mJ/cm2 low-pressure UV, and the in vitro TOP assay is a promising alternative to the mouse bioassay.

Derivatives of 5-Aminolevulinic Acid for Photodynamic Therapy

2007 ◽  
Vol 1 ◽  
pp. 1177391X0700100 ◽  
Author(s):  
Ryan F. Donnelly ◽  
Paul A. McCarron ◽  
David A. Woolfson
Keyword(s):  
Photodynamic Therapy ◽  
Side Effects ◽  
Aminolevulinic Acid ◽  
Skin Lesions ◽  
Rational Approach ◽  
Topical Formulation ◽  
Systemic Bioavailability ◽  
Clinical Benefits ◽  
Derivatives Of

Photodynamic therapy (PDT) is a clinical treatment that combines the effects of visible light irradiation with subsequent biochemical events that arise from the presence of a photosensitising drug (possessing no dark toxicity) to cause destruction of selected cells. Today, the most common agent used in dermatological PDT is 5-aminolevulinic acid (ALA). As a result of its hydrophilic character, ALA penetrates skin lesions poorly when applied topically. Its systemic bioavailability is limited and it is known to cause significant side effects when given orally or intravenously. Numerous chemical derivatives of ALA have been synthesised with the aims of either improving topical penetration or enhancing systemic bioavailability, while reducing side effects. In vitro cell culture experiments with ALA derivatives have yielded promising results. However, if ALA derivatives are to demonstrate meaningful clinical benefits, a rational approach to topical formulation design is required, along with a systematic study aimed at uncovering the true potential of ALA derivatives in photodynamic therapy. With respect to systemic ALA delivery, more study is required in the developing area of ALA-containing dendrons and dendrimers.

scholarly journals Anti- Toxoplasma gondii effect of Lumefantrine in vitro and in vivo

2020 ◽  
Author(s):  
Dawei Wang ◽  
Mengen Xing ◽  
Saeed El-Ashram ◽  
Yingying Ding ◽  
Xiaoyu Sang ◽  
...  
Keyword(s):  
Side Effects ◽  
Toxoplasma Gondii ◽  
Mtt Assay ◽  
Vero Cells ◽  
Protective Mechanism ◽  
High Dose ◽  
Mouse Tissues ◽  
Ifn Γ

Abstract Background: Toxoplasma gondii is an obligate intracellular protozoan parasite, which can infect almost all warm-blooded animals, including humans, leading to toxoplasmosis. Currently, the effective treatment for human toxoplasmosis is the combination of sulfadiazine and pyrimethamine. However, both drugs have serious side effects and toxicity in the host. Therefore, there is an urgent need for the discovery of new anti-Toxoplasma drugs with high potency and less or no side-effects. Methods: The cytotoxicity of sulfadiazine and lumefantrine to Vero cells was evaluated by the methyl thiazolyl tetrazolium (MTT) assay. And MTT assay was also used to detect the inhibitory effects of lumefantrine on parasites invasion and proliferation. Flow cytometry was conducted to further verify parasites proliferation. qPCR was performed to evaluate the parasite load in the mice after lumefantrine treatment. In order to determine whether lumefantrine treatment enhances Th1 or Th2 cytokine response, IFN-γ, IL-4, and IL-10 levels in the serum of mice were determined. Results: Our findings suggest that lumefantrine exerts activity against T. gondii by inhibiting its replication and invasion of Vero cells in vitro without being toxic to the cells. Furthermore, lumefantrine protected mice with acute toxoplasmosis from death to a certain extent and reduced the parasite burden in mouse tissues in vivo. In addition, a significant increase in IFN-γ production was observed in high dose lumefantrine-treated mice while IL-10 and IL-4 levels increased in low dose lumefantrine-treated mice. Conclusions: The results of this study demonstrated that lumefantrine may be a promising agent to treat toxoplamosis, and more experiments on the protective mechanism of lumefantrine should be undertaken in further studies.Key words: Toxoplasma gondii, Lumefantrine, anti-Toxoplasma gondii, Invasion, Proliferation

scholarly journals Possible replacement of cytokinins and auxins in culture in vitro

2019 ◽  
Vol 25 ◽  
pp. 293-297
Author(s):  
T. M. Oliynik ◽  
R. B. Kovbasenko ◽  
A. P. Dmitriev ◽  
P. G. Dulniev
Keyword(s):  
Cell Culture ◽  
Callus Tissue ◽  
Ms Medium ◽  
Pyridine Derivatives ◽  
Culture In Vitro ◽  
Somaclonal Variability ◽  
Proposed Modification ◽  
New Generation ◽  
Derivatives Of

Aim. To perform an analysis of the effectiveness of our proposed modification of the classical MS medium in which auxin and cytokinin are replaced by derivatives of the class of tetrahydrothio-fendioxide and pyridine. Methods. In this study, the work with cell culture in vitro, in particular aseptic sprouting of seeds, microclonal reproduction, callusogenesis and initiation of various types of morphogenesis was carried out according to known techniques. Two varieties of potatoes (Slovyanka, Lugovskaya) and two varieties of tomato (Lagidny, Bobrytsky) were used to induce somaclonal variability. Results. The ability of preparations of tetrahydrothiophenedioxide and pyridine derivatives to perform the function of auxins and cytokinins in the MS medium in the callusogenesis of Solanacea cultures in vitro was established. Conclusions. It has been shown that with the use of the new generation drug (tetrahydrothiophenedioxide-pyridine), as a substitute for auxin and cytokinin in the MS medium, the growth of callus tissue is even increased. The production of the pilot batch of this substitute proved to be much cheaper than synthesis or the purchase of phytohormones. Keywords: modification of MS medium, phytohormones substitute, tetrahydro-thiophenedioxide-pyridine, potato, tomato.

Synthesis of novel 1,3,4-oxadiazole derivatives of nicotinic acid and its in-vitro antithrombotic activity

2021 ◽  
pp. 431-434
Author(s):  
Vishal T. Khot ◽  
S. K. Mohite ◽  
C. S. Magdum
Keyword(s):  
Side Effects ◽  
Nicotinic Acid ◽  
Clot Formation ◽  
Activity Profile ◽  
Antithrombotic Activity ◽  
Oxadiazole Derivatives ◽  
Derivatives Of

The pharmacological characteristics of azole are diverse. Only a few medications can reduce the risk of clot formation, and they all have serious side effects. At present time there has to be more focus on to cure this type of complication beacause due to environmental, emotional, physical, other biological incidents are much related to this condition. Resistance has developed to existing medications, prompting the implementation of novel medications with a greater activity profile. The synthesis of a 1,3,4-oxadiazole derivative from nicotinic acid as well as its antithrombotic activity is described in this paper.

Sign in / Sign up

Export Citation Format

Share Document