Multi-Anti-Parasitic Activity of Arylidene Ketones and Thiazolidene Hydrazines against Trypanosoma cruzi and Leishmania spp.

被引：22

作者：

Alvarez, Guzman ^{[1
]}

Perdomo, Cintya ^{[1
]}

Coronel, Cathia ^{[2
]}

Aguilera, Elena ^{[3
]}

Varela, Javier ^{[3
]}

Aparicio, Gonzalo ^{[4
,5
]}

Zolessi, Flavio R. ^{[4
,5
]}

Cabrera, Nallely ^{[6
]}

Vega, Celeste ^{[2
]}

Rolon, Miriam ^{[2
]}

de Arias, Antonieta Rojas ^{[2
]}

Perez-Montfort, Ruy ^{[6
]}

Cerecetto, Hugo ^{[3
]}

Gonzalez, Mercedes ^{[3
]}

机构：

[1] Univ Republ, CENUR Litoral Norte, Lab Mol Bioact, Ruta 3 Km 363, Paysandu 60000, Uruguay

[2] CEDIC, FMB, Ctr Desarrollo Invest Cient, Diaz Gill Med Lab, Asuncion 1255, Paraguay

[3] Univ Republica, Fac Ciencias, Lab Quim Organ, Grp Quim Med, Montevideo 11400, Uruguay

[4] Univ Republica, Fac Ciencias, Secc Biol Celular, Montevideo 11400, Uruguay

[5] Inst Pasteur Montevideo, Cell Biol Neural Dev Lab, Montevideo 11400, Uruguay

[6] Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Bioquim & Biol Estruct, Mexico City 04510, DF, Mexico

来源：

MOLECULES | 2017年 / 22卷 / 05期

关键词：

anti-T. cruzi and anti-Leishmania spp. activity; arylidene ketones; thiazolidene hydrazines; triosephosphate isomerase; cruzipain; in vivo toxicity; zebrafish; CHRONIC CHAGAS-DISEASE; ZEBRAFISH DANIO-RERIO; IN-VIVO ACTIVITY; TRIOSEPHOSPHATE ISOMERASE; DEVELOPMENTAL TOXICITY; INHIBITORS; DISCOVERY; BIOACCUMULATION; IDENTIFICATION; EMBRYO;

D O I：

10.3390/molecules22050709

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of fifty arylideneketones and thiazolidenehydrazines was evaluated against Leishmania infantum and Leishmania braziliensis. Furthermore, new simplified thiazolidenehydrazine derivatives were evaluated against Trypanosoma cruzi. The cytotoxicity of the active compounds on non-infected fibroblasts or macrophages was established in vitro to evaluate the selectivity of their anti-parasitic effects. Seven thiazolidenehydrazine derivatives and ten arylideneketones had good activity against the three parasites. The IC50 values for T. cruzi and Leishmania spp. ranged from 90 nM-25 mu M. Eight compounds had multi-trypanocidal activity against T. cruzi and Leishmania spp. (the etiological agents of cutaneous and visceral forms). The selectivity of these active compounds was better than the three reference drugs: benznidazole, glucantime and miltefosine. They also had low toxicity when tested in vivo on zebrafish. Trying to understand the mechanism of action of these compounds, two possible molecular targets were investigated: triosephosphate isomerase and cruzipain. We also used a molecular stripping approach to elucidate the minimal structural requirements for their anti-T. cruzi activity.

引用

页数：26

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