Antileishmanial Activity of 1,3,4-Thiadiazolium-2-Aminide in Mice Infected with<i>Leishmania amazonensis</i>

Rodrigues, Renata; Charret, Karen S.; Silva, Edson F. da; Echevarrı́a, Aurea; Amaral, Verônica F.; Leon, Leonor L.; Canto‐Cavalheiro, Marilene M.

doi:10.1128/aac.00062-08

Cited by 12 publications

(19 citation statements)

References 23 publications

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“…Some mesoionic derivatives such as 42, 43, 44 and 45 have already been studied to determine their antiparasitic activity and very potent or potent antileishmanial activities have been shown for all derivatives against three Leishmania species (L. amazonensis, L. braziliensis and L. chagasi) as compared to pentamidine as a standard drug (48,95,96). Their effect on the TryR activity of three Leishmania species was also investigated and the nitroderivative (45) provided very promising results (89).…”

Section: -Amino-134-thiadiazole Derivatives As Trypanothione Reducmentioning

confidence: 99%

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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Section: -Amino-134-thiadiazole Derivatives As Trypanothione Reducmentioning

confidence: 99%

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

Şerban

2020

Acta Pharmaceutica

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“…Additionally, in vivo studies made in the mouse L. amazonensis cutaneous infection model showed that the 4-methoxy derivative 38 exhibited comparable activity to the reference drug, meglumine antimoniate [70]. The derivative 38 was more effective than the non-substituted derivative 37 .…”

Section: Antileishmanial Activity Associated With 2-amino-134-thmentioning

confidence: 99%

“…At the 10th week post infection, there was an increased difference in footpad swelling between the mice treated with the test compound 38 (derivative 38 , lesion size ≈ 3 mm; derivative 37 , lesion size ≈ 6 mm) or meglumine antimoniate (lesion size ≈ 4 mm) and untreated infected mice (lesion size ≈ 7 mm), respectively. At the 12th week post infection, the results showed significantly differences between the groups of mice treated with test compounds (derivative 38 , lesion size ≈ 6 mm; derivative 37 , lesion size ≈ 9 mm) or meglumine antimoniate (lesion size ≈ 7 mm) and untreated infected mice (lesion size ≈ 14 mm), respectively [70]. The authors concluded that no significant differences in lesion size were observed in the groups treated with mesoionic compounds or meglumine antimoniate [70].…”

Section: Antileishmanial Activity Associated With 2-amino-134-thmentioning

confidence: 99%

“…At the 12th week post infection, the results showed significantly differences between the groups of mice treated with test compounds (derivative 38 , lesion size ≈ 6 mm; derivative 37 , lesion size ≈ 9 mm) or meglumine antimoniate (lesion size ≈ 7 mm) and untreated infected mice (lesion size ≈ 14 mm), respectively [70]. The authors concluded that no significant differences in lesion size were observed in the groups treated with mesoionic compounds or meglumine antimoniate [70].…”

Section: Antileishmanial Activity Associated With 2-amino-134-thmentioning

confidence: 99%

“…The number of parasites in both lymph nodes and spleens of animals treated with mesoionic derivatives or meglumine antimoniate were significantly reduced compared to those of untreated control animals. In both cases, the reduction in the number of parasites after treatment with mesoionic derivatives was greater than that observed after meglumine antimoniate treatment (i.e., the number of parasites/mg tissue of lymph node in untreated animals ≈ 13,000, the number of parasites/mg tissue of lymph node in animals treated with meglumine antimoniate ≈ 3000, the number of parasites/mg tissue of lymph node in animals treated with mesoionic derivatives 37 or 38 < 1000, respectively) [70]. This suggests that there is a control of infection progression and the dissemination is limited.…”

Section: Antileishmanial Activity Associated With 2-amino-134-thmentioning

confidence: 99%

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Future Prospects in the Treatment of Parasitic Diseases: 2-Amino-1,3,4-Thiadiazoles in Leishmaniasis

Şerban

2019

Molecules

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Neglected tropical diseases affect the lives of a billion people worldwide. Among them, the parasitic infections caused by protozoan parasites of the Trypanosomatidae family have a huge impact on human health. Leishmaniasis, caused by Leishmania spp., is an endemic parasitic disease in over 88 countries and is closely associated with poverty. Although significant advances have been made in the treatment of leishmaniasis over the last decade, currently available chemotherapy is far from satisfactory. The lack of an approved vaccine, effective medication and significant drug resistance worldwide had led to considerable interest in discovering new, inexpensive, efficient and safe antileishmanial agents. 1,3,4-Thiadiazole rings are found in biologically active natural products and medicinally important synthetic compounds. The thiadiazole ring exhibits several specific properties: it is a bioisostere of pyrimidine or benzene rings with prevalence in biologically active compounds; the sulfur atom increases lipophilicity and combined with the mesoionic character of thiadiazoles imparts good oral absorption and good cell permeability, resulting in good bioavailability. This review presents synthetic 2-amino-1,3,4-thiadiazole derivatives with antileishmanial activity. Many reported derivatives can be considered as lead compounds for the synthesis of future agents as an alternative to the treatment of leishmaniasis.

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Investigation of trypanothione reductase inhibitory activity by 1,3,4-thiadiazolium-2-aminide derivatives and molecular docking studies

Rodrigues

Castro‐Pinto

Echevarrı́a

et al. 2012

Bioorganic & Medicinal Chemistry

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The biological activities of a series of mesoionic 1,3,4-thiadiazolium-2-aminide derivatives have been studied. The most active compounds (MI-HH; MI-3-OCH(3); MI-4-OCH(3) and MI-4-NO(2)) were evaluated to determine their effect on trypanothione reductase (TryR) activity in Leishmania sp. and Trypanosoma cruzi. Among the assayed compounds, only MI-4-NO(2) showed enzyme inhibition effect on extracts from different cultures of parasites, which was confirmed using the recombinant enzyme from T. cruzi (TcTryR) and Leishmania infantum (LiTryR). The enzyme kinetics determined with LiTryR demonstrated a non-competitive inhibition profile of MI-4-NO(2). A molecular docking study showed that the mesoionic compounds could effectively dock into the substrate binding site together with the substrate molecule. The mesoionic compounds were also effective ligands of the NADPH and FAD binding sites and the NADPH binding site was predicted as the best of all three binding sites. Based on the theoretical results, an explanation at the molecular level is proposed for the MI-4-NO(2) enzyme inhibition effect. Given TryR as a molecular target, it is important to continue the study of mesoionic compounds as part of a drug discovery campaign against Leishmaniasis or Chagas' disease.

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Antileishmanial Activity of 1,3,4-Thiadiazolium-2-Aminide in Mice Infected withLeishmania amazonensis

Cited by 12 publications

References 23 publications

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

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

Future Prospects in the Treatment of Parasitic Diseases: 2-Amino-1,3,4-Thiadiazoles in Leishmaniasis

Investigation of trypanothione reductase inhibitory activity by 1,3,4-thiadiazolium-2-aminide derivatives and molecular docking studies

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