Next Article in Journal
Manifestations of Age on Autophagy, Mitophagy and Lysosomes in Skeletal Muscle
Previous Article in Journal
Remdesivir and Ledipasvir among the FDA-Approved Antiviral Drugs Have Potential to Inhibit SARS-CoV-2 Replication
Article

1,3,4-Thiadiazoles Effectively Inhibit Proliferation of Toxoplasma gondii

1
Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland
2
Department of Molecular Microbiology, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland
3
Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland
4
Department of Pharmacology, Faculty of Health Sciences, Medical University of Lublin, Chodzki 4a, 20-093 Lublin, Poland
5
Institute of Applied Radiation Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland
6
International Centre for Research on Innovative Biobased Materials (ICRI-BioM)—International Research Agenda, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland
*
Authors to whom correspondence should be addressed.
Academic Editors: Alexander E. Kalyuzhny and John Buolamwini
Cells 2021, 10(5), 1053; https://doi.org/10.3390/cells10051053
Received: 24 March 2021 / Revised: 15 April 2021 / Accepted: 26 April 2021 / Published: 29 April 2021
Congenital and acquired toxoplasmosis caused by the food- and water-born parasite Toxoplasma gondii (T. gondii) is one of the most prevalent zoonotic infection of global importance. T. gondii is an obligate intracellular parasite with limited capacity for extracellular survival, thus a successful, efficient and robust host cell invasion process is crucial for its survival, proliferation and transmission. In this study, we screened a series of novel 1,3,4-thiadiazole-2-halophenylamines functionalized at the C5 position with the imidazole ring (1b12b) for their effects on T. gondii host cell invasion and proliferation. To achieve this goal, these compounds were initially subjected to in vitro assays to assess their cytotoxicity on human fibroblasts and then antiparasitic efficacy. Results showed that all of them compare favorably to control drugs sulfadiazine and trimethoprim in terms of T. gondii growth inhibition (IC50) and selectivity toward the parasite, expressed as selectivity index (SI). Subsequently, the most potent of them with meta-fluoro 2b, meta-chloro 5b, meta-bromo 8b, meta-iodo 11b and para-iodo 12b substitution were tested for their efficacy in inhibition of tachyzoites invasion and subsequent proliferation by direct action on established intracellular infection. All the compounds significantly inhibited the parasite invasion and intracellular proliferation via direct action on both tachyzoites and parasitophorous vacuoles formation. The most effective was para-iodo derivative 12b that caused reduction in the percentage of infected host cells by 44% and number of tachyzoites per vacuole by 93% compared to non-treated host cells. Collectively, these studies indicate that 1,3,4-thiadiazoles 1b12b, especially 12b with IC50 of 4.70 µg/mL and SI of 20.89, could be considered as early hit compounds for future design and synthesis of anti-Toxoplasma agents that effectively and selectively block the invasion and subsequent proliferation of T. gondii into host cells. View Full-Text
Keywords: 1,3,4-thiadiazole; cytotoxicity; genotoxicity; Toxoplasma gondii; SAR analysis 1,3,4-thiadiazole; cytotoxicity; genotoxicity; Toxoplasma gondii; SAR analysis
Show Figures

Figure 1

MDPI and ACS Style

Węglińska, L.; Bekier, A.; Dzitko, K.; Pacholczyk-Sienicka, B.; Albrecht, Ł.; Plech, T.; Paneth, P.; Paneth, A. 1,3,4-Thiadiazoles Effectively Inhibit Proliferation of Toxoplasma gondii. Cells 2021, 10, 1053. https://doi.org/10.3390/cells10051053

AMA Style

Węglińska L, Bekier A, Dzitko K, Pacholczyk-Sienicka B, Albrecht Ł, Plech T, Paneth P, Paneth A. 1,3,4-Thiadiazoles Effectively Inhibit Proliferation of Toxoplasma gondii. Cells. 2021; 10(5):1053. https://doi.org/10.3390/cells10051053

Chicago/Turabian Style

Węglińska, Lidia, Adrian Bekier, Katarzyna Dzitko, Barbara Pacholczyk-Sienicka, Łukasz Albrecht, Tomasz Plech, Piotr Paneth, and Agata Paneth. 2021. "1,3,4-Thiadiazoles Effectively Inhibit Proliferation of Toxoplasma gondii" Cells 10, no. 5: 1053. https://doi.org/10.3390/cells10051053

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop