Design, synthesis and biological evaluation of hybrid bioisoster derivatives of N-acylhydrazone and furoxan groups with potential and selective anti-Trypanosoma cruzi activity

被引：53

作者：

Massarico Serafim, Ricardo Augusto ^{[1
]}

Goncalves, Jose Eduardo ^{[2
]}

de Souza, Felipe Pereira ^{[3
]}

de Melo Loureiro, Ana Paula ^{[3
]}

Storpirtis, Silvia ^{[2
]}

Krogh, Renata ^{[4
]}

Andricopulo, Adriano Defini ^{[4
]}

Dias, Luiz Carlos ^{[5
]}

Ferreira, Elizabeth Igne ^{[1
]}

机构：

[1] Univ Sao Paulo, LAPEN Lab Planejamento & Sintese Quimioterap Pote, Fac Ciencias Farmaceut, Dept Farm, BR-05508900 Sao Paulo, Brazil

[2] Univ Sao Paulo, LPFCC, Fac Ciencias Farmaceut, Dept Farm, BR-05508900 Sao Paulo, Brazil

[3] Univ Sao Paulo, Dept Anal Clin & Toxicol, BR-05508900 Sao Paulo, Brazil

[4] Univ Sao Paulo, Inst Fis Sao Carlos, Ctr Pesquisa & Inovacao Biodiversidade & Farmacos, LQMC, Sao Carlos, SP, Brazil

[5] Univ Estadual Campinas UNICAMP, Inst Quim, LQOS, Campinas, SP, Brazil

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 82卷

基金：

巴西圣保罗研究基金会;

关键词：

Anti-Trypanosoma cruzi compounds; Molecular hybrids; Bioisosters; Nitric oxide donor groups; N-acylhydrazone derivatives; Furoxan derivatives; UNSYMMETRICALLY SUBSTITUTED FUROXANS; CHAGAS-DISEASE; TRYPANOCIDAL ACTIVITY; PERSPECTIVES; AGENTS; DRUGS;

D O I：

10.1016/j.ejmech.2014.05.077

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Hybrid bioisoster derivatives from N-acylhydrazones and furoxan groups were designed with the objective of obtaining at least a dual mechanism of action: cruzain inhibition and nitric oxide (NO) releasing activity. Fifteen designed compounds were synthesized varying the substitution in N-acylhydrazone and in furoxan group as well. They had its anti-Trypanosoma cruzi activity in amastigotes forms, NO releasing potential and inhibitory cruzain activity evaluated. The two most active compounds (6,14) both in the parasite amastigotes and in the enzyme contain the nitro group in para position of the aromatic ring. The permeability screening in Caco-2 cell and cytotoxicity assay in human cells were performed for those most active compounds and both showed to be less cytotoxic than the reference drug, benznidazole. Compound 6 was the most promising, since besides activity it showed good permeability and selectivity index, higher than the reference drug. Thereby the compound 6 was considered as a possible candidate for additional studies. (C) 2014 Elsevier Masson SAS. All rights reserved.

引用

页码：418 / 425

页数：8

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