الفهرس 
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Abstract
Toxoplasmosis is a zoonotic disease and a global food and water-borne infection. The disease is caused by the parasite T.gondii, which is a highly successful and remarkable pathogen because of its ability to infect almost any nucleated cell in warm-blooded animals.
Currently, combination of pyrimethamine and sulfadiazine serves as the first line treatment, however, these drugs have serious adverse effects. Therefore there is avital need to focus on new therapies that produce the desired effect with the lowest possible dose to minimize the risk of drug-drug interactions and multiple drug resistance. The molecular structural hybridization, in which two distinct active pharmacophores are linked together in a simple way to discover new drugs. Three compounds of 1,2,3-triazoles-based sulfonamide scaffold 3(a-c) were designed, synthesized and fully characterized in order to test their toxoplasmacidal effectiveness in vitro. Moreover, the synthesized compounds were loaded onto chitosan nanoparticles (CNPs) to create unique nano-formulations (3a.CNP, 3b.CNP, and 3c.CNP).The nano formulations were used to improve the synthesized compounds’ activity in terms of their solubility and cell membrane penetration to increase their effectiveness against the parasites.
In vitro cytotoxicity, anti-Toxoplasma activity, selectivity index of the prepared materials 3 (a-c), their nano-formulae 3a-c.CNP and the chitosan nanoparticles (CNP) were studied versus sulfadiazine. All the tested compounds had more potent activity against T. gondii compared to that exhibited by the sulfadiazine as drug control.The derivative 3c-CNP was discovered to have the highest activity against T. gondii and the greatest selectivity index, with an IC50 value of 3.64 µg/ml and a selectivity index of 38.7.
Microscopic techniques were used to observe cell morphology and enhance the understanding of in vitro anti-parasitic activity. To investigate the anti-Toxoplasma impact of the evaluated sulfadrug-based 1,2,3-triazoles 3(a,b,c) and their nano-formulae 3a-c.CNP,
we were employed light and scanning electron microscopes examination (SEM). All of the examined substances had a significant impact on the morphology of treated tachyzoites, but 3c.CNP displayed numerous surface depressions as well as a fully deformed morphology. Additionally, transmission electron microscopy (TEM) analysis was done to determine the underlying mechanism of action of all tested drugs on the intracellular tachyzoite. Each substance significantly altered the ultrastructure of the cells, causing cytoplasmic vacuolations to emerge, parasite organelles to vanish, and apical complex structures to be disrupted. The compound 3c.CNP caused the most pronounced alterations, causing organelles to totally vanish and the nuclear membrane to lyse, utterly disrupting tachyzoites. Due to the discharge of cytoplasmic contents from the damaged tachyzoites’ cytoplasmic membranes, the tubulovesicular network looked black and granular.