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Cell death and ultrastructural alterations in Leishmania amazonensis caused by new compound 4-Nitrobenzaldehyde thiosemicarbazone derived from S-limonene
被引:61
作者:

Britta, Elizandra Aparecida
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Univ Estadual Maringa, Programa Posgrad Ciencias Farmaceut, BR-5790 Maringa, PR, Brazil Univ Estadual Maringa, Programa Posgrad Ciencias Farmaceut, BR-5790 Maringa, PR, Brazil

Scariot, Debora Botura
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Univ Estadual Maringa, Programa Posgrad Ciencias Farmaceut, BR-5790 Maringa, PR, Brazil Univ Estadual Maringa, Programa Posgrad Ciencias Farmaceut, BR-5790 Maringa, PR, Brazil

Falzirolli, Hugo
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Univ Estadual Maringa, Dept Quim, BR-5790 Maringa, PR, Brazil Univ Estadual Maringa, Programa Posgrad Ciencias Farmaceut, BR-5790 Maringa, PR, Brazil

Ueda-Nakamura, Tania
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Univ Estadual Maringa, Programa Posgrad Ciencias Farmaceut, BR-5790 Maringa, PR, Brazil Univ Estadual Maringa, Programa Posgrad Ciencias Farmaceut, BR-5790 Maringa, PR, Brazil

Silva, Cleuza Conceicao
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Univ Estadual Maringa, Dept Quim, BR-5790 Maringa, PR, Brazil Univ Estadual Maringa, Programa Posgrad Ciencias Farmaceut, BR-5790 Maringa, PR, Brazil

Dias Filho, Benedito Prado
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Univ Estadual Maringa, Programa Posgrad Ciencias Farmaceut, BR-5790 Maringa, PR, Brazil Univ Estadual Maringa, Programa Posgrad Ciencias Farmaceut, BR-5790 Maringa, PR, Brazil

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Nakamura, Celso Vataru
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Univ Estadual Maringa, Programa Posgrad Ciencias Farmaceut, BR-5790 Maringa, PR, Brazil Univ Estadual Maringa, Programa Posgrad Ciencias Farmaceut, BR-5790 Maringa, PR, Brazil
机构:
[1] Univ Estadual Maringa, Programa Posgrad Ciencias Farmaceut, BR-5790 Maringa, PR, Brazil
[2] Univ Estadual Maringa, Dept Quim, BR-5790 Maringa, PR, Brazil
[3] Univ Grenoble Alpes, CERMAV, CNRS, UPR 5301, F-38000 Grenoble, France
来源:
关键词:
Antileishmanial activity;
Benzaldehyde thiosemicarbazone;
Leishmania amazonensis;
Ultrastructural alterations;
Mitochondria damage;
Electron microscopy;
Cellular disorganization;
MITOCHONDRIAL DYSFUNCTION;
BIOLOGICAL-ACTIVITY;
TRYPANOCIDAL ACTION;
AMASTIGOTE FORMS;
IN-VITRO;
INHIBITION;
BIOSYNTHESIS;
DERIVATIVES;
D O I:
10.1186/s12866-014-0236-0
中图分类号:
Q93 [微生物学];
学科分类号:
071005 ;
100705 ;
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 mu M, respectively. Intracellular amastigotes were inhibited by the compound with an IC50 of 7.7 mu M. BZTS also had a CC50 of 88.8 mu 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.
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Univ Estadual Maringa, Postgrad Program Pharmaceut Sci, BR-87020900 Maringa, Parana, Brazil Univ Estadual Maringa, Postgrad Program Pharmaceut Sci, BR-87020900 Maringa, Parana, Brazil

Sudatti, Daniela Bueno
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Univ Fed Fluminense, Dept Marine Biol, BR-24001970 Rio De Janeiro, Brazil Univ Estadual Maringa, Postgrad Program Pharmaceut Sci, BR-87020900 Maringa, Parana, Brazil

Pereira, Renato Crespo
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Univ Fed Fluminense, Dept Marine Biol, BR-24001970 Rio De Janeiro, Brazil Univ Estadual Maringa, Postgrad Program Pharmaceut Sci, BR-87020900 Maringa, Parana, Brazil

Alonso, Antonio
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Univ Fed Goias, Inst Phys, BR-74001970 Goiania, Go, Brazil Univ Estadual Maringa, Postgrad Program Pharmaceut Sci, BR-87020900 Maringa, Parana, Brazil

Ueda-Nakamura, Tania
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Univ Estadual Maringa, Postgrad Program Pharmaceut Sci, BR-87020900 Maringa, Parana, Brazil
Univ Estadual Maringa, Dept Basic Hlth Sci, BR-87020900 Maringa, Parana, Brazil Univ Estadual Maringa, Postgrad Program Pharmaceut Sci, BR-87020900 Maringa, Parana, Brazil

Dias Filho, Benedito Prado
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Univ Estadual Maringa, Postgrad Program Pharmaceut Sci, BR-87020900 Maringa, Parana, Brazil
Univ Estadual Maringa, Dept Basic Hlth Sci, BR-87020900 Maringa, Parana, Brazil Univ Estadual Maringa, Postgrad Program Pharmaceut Sci, BR-87020900 Maringa, Parana, Brazil

Nakamura, Celso Vataru
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Univ Estadual Maringa, Postgrad Program Pharmaceut Sci, BR-87020900 Maringa, Parana, Brazil
Univ Estadual Maringa, Dept Basic Hlth Sci, BR-87020900 Maringa, Parana, Brazil Univ Estadual Maringa, Postgrad Program Pharmaceut Sci, BR-87020900 Maringa, Parana, Brazil

Silva, Sueli de Oliveira
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Univ Estadual Maringa, Postgrad Program Pharmaceut Sci, BR-87020900 Maringa, Parana, Brazil
Univ Estadual Maringa, Dept Basic Hlth Sci, BR-87020900 Maringa, Parana, Brazil Univ Estadual Maringa, Postgrad Program Pharmaceut Sci, BR-87020900 Maringa, Parana, Brazil