New iminodibenzyl derivatives with anti-leishmanial activity

被引：6
作者：
Arndt, Anderson [1 ]
Liria, Cleber Wanderlei [2 ]
Yokoyama-Yasunaka, Jenicer K. U. [3 ]
Teresa Machini, M. [2 ]
Bortolin Uhana, Silvia Reni [3 ]
Esposito, Breno Pannia [1 ]
机构：
[1] Univ Sao Paulo, Dept Fundamental Chem, Av Prof Lineu Prestes 748, BR-05508000 Sao Paulo, SP, Brazil
[2] Univ Sao Paulo, Dept Biochem, Inst Chem, Av Prof Lineu Prestes 748, BR-05508000 Sao Paulo, SP, Brazil
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Av Prof Lineu Prestes 1374, BR-05508000 Sao Paulo, SP, Brazil
来源：
JOURNAL OF INORGANIC BIOCHEMISTRY | 2017年 / 172卷
基金：
巴西圣保罗研究基金会;
关键词：
Copper; Iminodibenzyl; Leishmania; Chelation therapy;
D O I：
10.1016/j.jinorgbio.2017.04.004
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：
Leishmaniasis is an infection caused by protozoa of the genus Leishmania and transmitted by sandflies. Current treatments are expensive and time-consuming, involving Sb(V)-based compounds, lipossomal amphotericin B and miltefosine. Recent studies suggest that inhibition of trypanothione reductase (TR) could be a specific target in the development of new drugs because it is essential and exclusive to trypanosomatids. This work presents the synthesis and characterization of new iminodibenzyl derivatives (dado) with ethylenediamine (ea), ethanolamine (en) and diethylenetriamine (dien) and their copper(II) complexes. Computational methods indicated that the complexes were highly lipophilic. Pro-oxidant activity assays by oxidation of the dihydrorhodamine (DHR) fluorimetric probe showed that [Cu(dado-ea)](2+) has the highest rate of oxidation, independent of H2O2 concentration. The toxicity to L. amazonensis promastigotes and RAW 264,7 macrophages was assessed, showing that dado-en was the most active new compound. Complexation to copper did not have an appreciable effect on the toxicity of the compounds.
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页码：9 / 15
页数：7
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