In vitro effect of a novel protease inhibitor cocktail on Toxoplasma gondii tachyzoites

Elkerdany, Eman D.; el-Nassery, S M; Arafa, Fadwa M.; Zaki, Sahar Abdel-fattah; Mady, Rasha Fadly

doi:10.1016/j.exppara.2020.108010

Cited by 3 publications

(4 citation statements)

References 34 publications

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“…Normally, the host cell supplies nutrition to the parasite through the formation of a network of tubules and vesicles (the tubulovesicular network). This disintegrated granular appearance after treatment could be explained by the leakage of the cytoplasmic contents through the disrupted cytoplasmic membrane of affected tachyzoites (Elkerdany et al 2020 ). Thus, it can be assumed that treatment compromised the integrity of this essential network and its surrounding membrane.…”

Section: Discussionmentioning

confidence: 99%

Sulfadiazine analogs: anti-Toxoplasma in vitro study of sulfonamide triazoles

Arafa,

Osman,

Tolba

et al. 2023

Parasitol Res

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Toxoplasmosis is an infection that prevails all over the world and is caused by the obligate intracellular protozoan parasite Toxoplasma gondii (T. gondii). Promising novel compounds for the treatment of T. gondii are introduced in the current investigation. In order to test their in vitro potency against T. gondii tachyzoites, six 1,2,3-triazoles-based sulfonamide scaffolds with terminal NH2 or OH group were prepared and investigated as sulfadiazine equivalents. When compared to sulfadiazine, which served as a positive control, hybrid molecules showed much more anti-Toxoplasma activity. The results showed that the IC50 of the examined compounds 3(a–f) were recoded as 0.07492 μM, 0.07455 μM, 0.0392 μM, 0.03124 μM, 0.0533 μM, and 0.01835 μM, respectively, while the sulfadiazine exhibited 0.1852 μM. The studied 1,2,3-triazole-sulfadrug molecular conjugates 3(a–f) revealed selectivity index of 10.4, 8.9, 25.4, 21, 8.3, and 29; respectively. The current study focused on the newly synthesized amino derivatives 3(d–f), as they contain the more potent amino groups which are recognized to be essential elements and promote better biological activity. Extracellular tachyzoites underwent striking morphological alterations after 2 h of treatment as seen by scanning electron microscopy (SEM). Additionally, the intracellular tachyzoite exposed to the newly synthesized amino derivatives 3(d–f) for a 24-h period of treatment revealed damaged and altered morphology by transmission electron microscopic (TEM) indicating cytopathic effects. Moreover, compound 3f underwent the most pronounced changes, indicating that it had the strongest activity against T. gondii.

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Section: Discussionmentioning

confidence: 99%

Sulfadiazine analogs: anti-Toxoplasma in vitro study of sulfonamide triazoles

Arafa,

Osman,

Tolba

et al. 2023

Parasitol Res

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Section: Discussionmentioning

confidence: 99%

“…Intracellular multiplication is another function that helps the parasite increase its numbers to spread into neighboring cells. The tethered tachyzoites might suggest that the effect in already established infection was due to deformed daughter cell budding, leading to blocked intracellular development and eventually parasite dissemination [64,65] The most drastic changes were noticed with compound 3c.CNP, where tachyzoites were completely disrupted with complete disappearance of organelles and lysis of the nuclear membrane. The tubulovesicular network appeared dark and granular due to the release of cytoplasmic contents out of the disrupted cytoplasmic membranes of the affected tachyzoites [64], this together with a destabilized PV membrane might have allowed permeation of the host cell's cytoplasmic contents into the PV [62].…”

Section: Discussionmentioning

confidence: 99%

“…The tethered tachyzoites might suggest that the effect in already established infection was due to deformed daughter cell budding, leading to blocked intracellular development and eventually parasite dissemination [64,65] The most drastic changes were noticed with compound 3c.CNP, where tachyzoites were completely disrupted with complete disappearance of organelles and lysis of the nuclear membrane. The tubulovesicular network appeared dark and granular due to the release of cytoplasmic contents out of the disrupted cytoplasmic membranes of the affected tachyzoites [64], this together with a destabilized PV membrane might have allowed permeation of the host cell's cytoplasmic contents into the PV [62].…”

Section: Discussionmentioning

confidence: 99%

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Nanoformulation-Based 1,2,3-Triazole Sulfonamides for Anti-Toxoplasma In Vitro Study

et al. 2023

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Toxoplasma gondii is deemed a successful parasite worldwide with a wide range of hosts. Currently, a combination of pyrimethamine and sulfadiazine serves as the first-line treatment; however, these drugs have serious adverse effects. Therefore, it is imperative to focus on new therapies that produce the desired effect with the lowest possible dose. The designation and synthesis of sulfonamide-1,2,3-triazole hybrids (3a–c) were performed to create hybrid frameworks. The newly synthesized compounds were loaded on chitosan nanoparticles (CNPs) to form nanoformulations (3a.CNP, 3b.CNP, 3c.CNP) for further in vitro investigation as an anti-Toxoplasma treatment. The current study demonstrated that all examined compounds were active against T. gondii in vitro relative to the control drug, sulfadiazine. 3c.CNP showed the best impact against T. gondii with the lowest IC50 value of 3.64 µg/mL. Using light microscopy, it was found that Vero cells treated with the three nanoformulae showed remarkable morphological improvement, and tachyzoites were rarely seen in the treated cells. Moreover, scanning and transmission electron microscopic studies confirmed the efficacy of the prepared nanoformulae on the parasites. All of them caused parasite ultrastructural damage and altered morphology, suggesting a cytopathic effect and hence confirming their promising anti-Toxoplasma activity.

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