In vitro leishmanicidal activity of pyrazole-containing polyamine macrocycles which inhibit the Fe-SOD enzyme of Leishmania infantum and Leishmania braziliensis species

被引：13

作者：

Navarro, P. ^{[1
]}

Sanchez-Moreno, M. ^{[2
]}

Marin, C. ^{[2
]}

Garcia-Espana, E. ^{[3
]}

Ramirez-Macias, I. ^{[2
]}

Olmo, F. ^{[2
]}

Rosales, M. J. ^{[2
]}

Gomez-Contreras, F. ^{[4
]}

Yunta, M. J. R. ^{[4
]}

Gutierrez-Sanchez, R. ^{[5
]}

机构：

[1] CSIC, Inst Quim Med, Ctr Quim Organ M Lora Tamayo, E-28006 Madrid, Spain

[2] Univ Granada, Fac Ciencias, Dept Parasitol, E-18071 Granada, Spain

[3] Univ Valencia, Inst Ciencia Mol, Dept Quim Inorgan, E-46980 Paterna, Valencia, Spain

[4] Univ Complutense, Fac Quim, Dept Quim Organ, E-28040 Madrid, Spain

[5] Univ Granada, Fac Ciencias, Dept Estadist, E-18071 Granada, Spain

来源：

PARASITOLOGY | 2014年 / 141卷 / 08期

关键词：

Leishmania braziliensis; Leishmania infantum; iron superoxide dismutase; leishmanicidal activity; pyrazole; polyamine macrocycle; CONTAINING SUPEROXIDE-DISMUTASE; MACROBICYCLIC POLYAMINES; VISCERAL LEISHMANIASIS; MUCOSAL LEISHMANIASIS; ENERGY-METABOLISM; CHAGAS-DISEASE; IRON; TRYPANOSOMATIDS; DERIVATIVES; SIMULATION;

D O I：

10.1017/S0031182014000201

中图分类号：

R38 [医学寄生虫学]; Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ; 100103 ;

摘要：

The in vitro leishmanicidal activity and cytotoxicity of pyrazole-containing macrocyclic polyamines 1-4 was assayed on Leishmania infantum and Leishmania braziliensis species. Compounds 1-4 were more active and less toxic than glucantime and both infection rates and ultrastructural alterations confirmed that 1 and 2 were highly leishmanicidal and induced extensive parasite cell damage. Modifications in the excretion products of parasites treated with 1-3were also consistent with substantial cytoplasm alterations. Compound 2 was highlighted as a potent inhibitor of Fe-SOD in both species, whereas its effect on human CuZn-SOD was poor. Molecular modelling suggested that 2 could deactivate Fe-SOD due to a sterically favoured enhanced ability to interact with the H-bonding net that supports the enzyme's antioxidant features.

引用

页码：1031 / 1043

页数：13

共 3 条

[1] In vitro leishmanicidal activity of imidazole- or pyrazole-based benzo[g]phthalazine derivatives against Leishmania infantum and Leishmania braziliensis species
Sanchez-Moreno, Manuel
Gomez-Contreras, Fernando
Navarro, Pilar
Marin, Clotilde
Ramirez-Macias, Inmaculada
Olmo, Francisco
Maria Sanz, Ana
Campayo, Lucrecia
Cano, Carmen
Yunta, Maria J. R.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2012, 67 (02) : 387 - 397
[2] Imidazole-containing phthalazine derivatives inhibit Fe-SOD performance in Leishmania species and are active in vitro against visceral and mucosal leishmaniasis
Sanchez-Moreno, M.
Gomez-Contreras, F.
Navarro, P.
Marin, C.
Ramirez-Macias, I.
Rosales, M. J.
Campayo, L.
Cano, C.
Sanz, A. M.
Yunta, M. J. R.
PARASITOLOGY, 2015, 142 (08) : 1115 - 1129
[3] Imidazole-containing phthalazine derivatives inhibit Fe-SOD performance in Leishmania species and are active in vitro against visceral and mucosal leishmaniasis (vol 142, pg 1115, 2015)
Sanchez-Moreno, M.
Gomez-Contreras, F.
Navarro, P.
Marin, C.
Ramirez-Macias, I.
Rosales, M. J.
Campayo, L.
Cano, C.
Sanz, A. M.
Yunta, M. J. R.
PARASITOLOGY, 2015, 142 (10) : 1350 - 1350

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