Cell death and ultrastructural alterations in Leishmania amazonensis caused by new compound 4-Nitrobenzaldehyde thiosemicarbazone derived from S-limonene

BMC Microbiology

Celso Vataru Nakamura¹  Redouane Borsali³  Benedito Prado Dias Filho¹  Cleuza Conceição Silva²  Tânia Ueda-Nakamura¹  Hugo Falzirolli²  Débora Botura Scariot¹  Elizandra Aparecida Britta¹ 

[1] Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Avenida Colombo, Jd. Universitário, Maringá 5790, PR, Brazil;Departamento de Química, Universidade Estadual de Maringá, Maringá, PR, Brazil;Université Grenoble Alpes, CERMAV-CNRS UPR 5301, Grenoble F-38000, France

关键词: Cellular disorganization;    Electron microscopy;    Mitochondria damage;    Ultrastructural alterations;    Leishmania amazonensis;    Benzaldehyde thiosemicarbazone;    Antileishmanial activity;   

Others  :  1170527
DOI  :  10.1186/s12866-014-0236-0

 received in 2014-06-18, accepted in 2014-08-20,  发布年份 2014

【 摘 要 】

Background

The treatment of leishmaniasis with pentavalent antimonials is problematic because of their toxicity. Investigations of potentially active molecules are important to discover less toxic drugs that are viable economic alternatives for the treatment of leishmaniasis. Thiosemicarbazones are a group of molecules that are known for their wide versatility and biological activity. In the present study, we examined the antileishmania activity, mechanism of action, and biochemical alterations produced by a novel molecule, 4-nitrobenzaldehyde thiosemicarbazone (BZTS), derived from S-limonene against Leishmania amazonensis.

Results

BZTS inhibited the growth of the promastigote and axenic amastigote forms, with an IC₅₀ of 3.8 and 8.0 ?M, respectively. Intracellular amastigotes were inhibited by the compound with an IC₅₀ of 7.7 ?M. BZTS also had a CC₅₀ of 88.8 ?M for the macrophage strain J774A1. BZTS altered the shape, size, and ultrastructure of the parasites, including damage to mitochondria, reflected by extensive swelling and disorganization of the inner mitochondrial membrane, intense cytoplasmic vacuolization, and the presence of concentric membrane structures inside the organelle. Cytoplasmic lipid bodies, vesicles inside vacuoles in the flagellar pocket, and enlargement were also observed. BZTS did not induce alterations in the plasma membrane or increase annexin-V fluorescence intensity, indicating no phosphatidylserine exposure. However, it induced the production of mitochondrial superoxide anion radicals.

Conclusions

The present results indicate that BZTS induced dramatic effects on the ultrastructure of L. amazonensis, which might be associated with mitochondrial dysfunction and oxidative damage, leading to parasite death.

【 授权许可】

   
2014 Britta et al.; licensee BioMed Central Ltd.

【 图 表 】

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