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Biological evaluation of newly synthesized quinoline-based compound PPQ-8 in acute and chronic toxoplasmosis: An
Hanan Abd Elgawad1, Samar M Alhusseiny1, Amira Taman1
1Department of Medical Parasitology, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt.
Abstract:
Toxoplasma gondii is a widely distributed protozoan parasite, which affects worm-blooded animals including human. The commonest chemotherapeutics used for treatment of symptomatic toxoplasmosis have numerous adverse effects. Thus there is an eminent need to develop new therapeutic agents. Here we described the therapeutic efficacy of 4-(2-chloroquinolin-3-yl)-6-(2,5-dimethoxyphenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile (PPQ-8); a quinoline-related compound in a mouse model of acute and chronic toxoplasmosis. In acute infection, PPQ-8 decreased the parasite load in liver and spleen with amelioration of the hepatic and splenic pathology. In addition, recovered tachyzoites showed distorted shapes, reduced sizes, irregularities, surface protrusions, erosions and peeling besides apical region distortion when seen by scanning electron microscopy. In chronic toxoplasmosis, PPQ-8 produced degeneration and reduction of the brain cysts without stimulating a damaging inflammatory response within the brain. In both models acute and chronic, PPQ-8 prolonged the survival time of mice. These findings hold promise for the development of a novel anti-toxoplasmosis drug using PPQ-8, but further in vivo studies should be carried out to elucidate PPQ-8 mechanism of action and to report its efficacy in combination with other anti-toxoplasmosis agents.
Insights
A novel quinoline-related compound, PPQ-8, effectively reduced Toxoplasma gondii parasite load and pathology in acute and chronic mouse models. PPQ-8 also improved survival rates, showing promise as a new anti-toxoplasmosis therapeutic agent.
Area of Science:
- Parasitology
- Medicinal Chemistry
- Pharmacology
Background:
- Toxoplasma gondii is a widespread protozoan parasite affecting warm-blooded animals, including humans.
- Current treatments for toxoplasmosis have significant adverse effects, necessitating the development of new therapeutic agents.
- There is an unmet need for safer and more effective treatments for toxoplasmosis.
Purpose of the Study:
- To evaluate the therapeutic efficacy of a quinoline-related compound, PPQ-8, against acute and chronic Toxoplasma gondii infections in a mouse model.
- To assess the impact of PPQ-8 on parasite load, organ pathology, and survival.
- To investigate the effects of PPQ-8 on parasite morphology using scanning electron microscopy.
Main Methods:
- Administration of PPQ-8 to mice infected with Toxoplasma gondii.
- Assessment of parasite load in the liver and spleen during acute infection.
- Histopathological examination of liver and spleen tissues.
- Scanning electron microscopy to analyze tachyzoite morphology.
- Evaluation of brain cyst burden and inflammatory response in chronic infection.
- Monitoring of mouse survival rates in both acute and chronic models.
Main Results:
- PPQ-8 significantly decreased parasite load and ameliorated liver and spleen pathology in acute toxoplasmosis.
- Scanning electron microscopy revealed morphological alterations in tachyzoites treated with PPQ-8.
- In chronic toxoplasmosis, PPQ-8 reduced brain cyst burden without inducing detrimental inflammation.
- PPQ-8 treatment prolonged survival time in mice with both acute and chronic infections.
Conclusions:
- PPQ-8 demonstrates significant therapeutic efficacy against both acute and chronic Toxoplasma gondii infections in mice.
- The compound shows potential as a novel drug candidate for treating toxoplasmosis.
- Further in vivo studies are warranted to elucidate PPQ-8's mechanism of action and explore combination therapies.
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