1,4-Disubstituted Thiosemicarbazide Derivatives are Potent Inhibitors of Toxoplasma gondii Proliferation

Dzitko, Katarzyna; Paneth, Agata; Plech, Tomasz; Pawełczyk, Jakub; Stączek, Paweł; Stefańska, Joanna; Paneth, Piotr

doi:10.3390/molecules19079926

Cited by 26 publications

(28 citation statements)

References 52 publications

(72 reference statements)

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“…At the moment, very promising compounds seem to be also thiosemicarbazide derivatives [56], which, as shown in our recent studies, appear to limit in vitro multiplication of T. gondii, while being nontoxic to host cells. An IC 50 value obtained by us for sulfadiazine (control) was 15-fold higher than the value of one from the most active toward parasite compounds (IC 50 at 33.17 mg/ ml) [57].…”

Section: Other Synthetic Compoundsmentioning

confidence: 99%

Human toxoplasmosis–Searching for novel chemotherapeutics

Antczak

Dzitko

Długońska

2016

Biomedicine & Pharmacotherapy

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Section: Other Synthetic Compoundsmentioning

confidence: 99%

Human toxoplasmosis–Searching for novel chemotherapeutics

Antczak

Dzitko

Długońska

2016

Biomedicine & Pharmacotherapy

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“…According to WHO, it is estimated that 95 % of people with an immunocompetent system will not develop clinical symptoms when they are infected with T. gondii, or they may experience mild influenza--like symptoms such as fever, headache or myalgia that quickly pass (116). However, T. gondii can cause serious pathologies such as ocular disorders (e.g., eye infection, decreased visual acuity, retinochoroiditis) and severe neurological disorders (e.g., toxoplasmic encephalitis, mental retardation, necrotic lesions of central nervous system, epilepsy, and schizophrenia) in neonates and immune-suppressed individuals such as HIV-AIDS positive, cancer or organ transplant patients (113,117,118).…”

Section: Antitoxoplasmosis Activitymentioning

confidence: 99%

“…The current treatment for toxoplasmosis consists in the use of pyrimethamine (5) (DHFR inhibitor) and sulfonamides such as sulfamethoxazole (6) or sulfadiazine (dihydropteroate synthetase inhibitors), supplemented with folinic acid. The effectiveness of this treatment is limited by the large amounts of necessary drugs and serious sideeffects such as hypersensitivity, haematological toxicity, teratogenicity, allergic reactions, bone marrow suppression and liver toxicity that occur in long-term treatment (117,120). The treatment is also ineffective in removing the bradyzoite form of parasites located in the central nervous system (113,117,120).…”

Section: Antitoxoplasmosis Activitymentioning

confidence: 99%

“…The effectiveness of this treatment is limited by the large amounts of necessary drugs and serious sideeffects such as hypersensitivity, haematological toxicity, teratogenicity, allergic reactions, bone marrow suppression and liver toxicity that occur in long-term treatment (117,120). The treatment is also ineffective in removing the bradyzoite form of parasites located in the central nervous system (113,117,120). In order to reduce the transmission of parasite from mother to fetus, pregnant women can be treated with spiramycin, a macrolide antibiotic with low toxicity but limited activity against the parasite (59,113).…”

Section: Antitoxoplasmosis Activitymentioning

confidence: 99%

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2-Amino-1,3,4-thiadiazoles as prospective agents in trypanosomiasis and other parasitoses

Şerban

2020

Acta Pharmaceutica

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Parasitic diseases are a serious public health problem affecting hundreds of millions of people worldwide. African trypanosomiasis, American trypanosomiasis, leishmaniasis, malaria and toxoplasmosis are the main parasitic infections caused by protozoan parasites with over one million deaths each year. Due to old medications and drug resistance worldwide, there is an urgent need for new antiparasitic drugs. 1,3,4-Thiadiazoles have been widely studied for medical applications. The chemical, physical and pharmacokinetic properties recommend 1,3,4-thiadiazole ring as a target in drug development. Many scientific papers report the antiparasitic potential of 2-amino-1,3,4-thiadiazoles. This review presents synthetic 2-amino-1,3,4-thiadiazoles exhibiting antitrypanosomal, antimalarial and antitoxoplasmal activities. Although there are insufficient results to state the quality of 2-amino-1,3,4-thiadiazoles as a new class of antiparasitic agents, many reported derivatives can be considered as lead compounds for drug synthesis and a promise for the future treatment of parasitosis and provide a valid strategy for the development of potent antiparasitic drugs.

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“…CCL-2) cells, and inhibition of Toxoplasma (RH strain; ATCC no. 50174) growth were described elsewhere (8). The effect of tested compounds on the intensity of Toxoplasma gondii proliferation (%) was measured by 2 methods: incorporation of [ 3 H]uracil ( Fig.…”

mentioning

confidence: 99%

Triazole-Based Compound as a Candidate To Develop Novel Medicines To Treat Toxoplasmosis

Dzitko

Paneth

Plech

et al. 2014

Antimicrob Agents Chemother

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dThis article reports anti-Toxoplasma gondii activity of 3-(thiophen-2-yl)-1,2,4-triazole-5-thione. The compound displayed significant and reproducible antiparasitic effects at nontoxic concentrations for the host cells, with an experimentally determined 50% inhibitory concentration (IC 50 ) at least 30 times better than that of the known chemotherapeutic agent sulfadiazine. Purine nucleoside phosphorylase was defined as the probable target for anti-Toxoplasma activity of the tested compound. These results provide the foundation for future work to develop a new class of medicines to better treat toxoplasmosis. Standard chemotherapy for the treatment of Toxoplasma infections relies on the inhibition of folate metabolism. The protocol recommends synergistic combination of diaminopyrimidines with sulfonamides, supplemented with folinic acid to mitigate the toxic effects of pyrimethamine on bone marrow. For patients with sensitivity to sulfonamines, macrolides and lincosamides are a second class of medications with anti-Toxoplasma activity. The third class of anti-Toxoplasma drugs, which are only occasionally used as a potential substitute, comprises electron transport inhibitors such as atovaquone (1). In all of these situations, drug resistance, high cost, limited efficacy, and side effects of these drugs often result in discontinuation of therapy (2-5). Therefore, new agents with better activity profiles and that are less expensive are needed. One possible class of drugs are s-triazole derivatives, and in this article, we present a newly found triazole-based candidate to develop novel medicines for more effective treatment of toxoplasmosis.The search for agents that are potent and selective against Toxoplasma continues in several laboratories. Numerous inhibitors with activities in the nanomolar range with no appreciable in vitro toxicity to human cells have been identified. Examples are pyrimidines, oryzalines, thiazolidinones, berberines, tryptanthrines, thiocyanates, and bisphosphonates (6, 7). Our attention has been focused on the role of s-triazole series as potential new toxoplasmosis therapeutics. We found that 3-(thiophen-2-yl)-1,2,4-triazole-5-thione (compound 1) showed a potent and reproducible antiparasitic effect with no appreciable toxicity to human cells, while 4-ethyl-3-(4-methyl-1,2,3-thiadiazol-5-yl)-1,2,4-triazole-5-thione (compound 2) was inactive.The procedure for synthesis of 3-(thiophen-2-yl)-1,2,4-triazole-5-thione (compound 1) and 4-ethyl-3-(4-methyl-1,2,3-thiadiazol-5-yl)-1,2,4-triazole-5-thione (compound 2), the effects of tested compounds and sulfadiazine on the viability of L929 (ATCC no. CCL-1) and HeLa (ATCC no. CCL-2) cells, and inhibition of Toxoplasma (RH strain; ATCC no. 50174) growth were described elsewhere (8). The effect of tested compounds on the intensity of Toxoplasma gondii proliferation (%) was measured by 2 methods: incorporation of [ 3 H]uracil (Fig. 1) into the T. gondii DNA (9) and quantitative real-time PCR (qRT-PCR) (Fig. 1) (8). The 50% inhibitory concentration (I...

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1,4-Disubstituted Thiosemicarbazide Derivatives are Potent Inhibitors of Toxoplasma gondii Proliferation

Cited by 26 publications

References 52 publications

Human toxoplasmosis–Searching for novel chemotherapeutics

Human toxoplasmosis–Searching for novel chemotherapeutics

2-Amino-1,3,4-thiadiazoles as prospective agents in trypanosomiasis and other parasitoses

Triazole-Based Compound as a Candidate To Develop Novel Medicines To Treat Toxoplasmosis

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