Benzophenone derivatives as cysteine protease inhibitors and biological activity against Leishmania (L.) amazonensis amastigotes

被引：24

作者：

de Almeida, Leticia ^{[1
]}

Alves, Karina Ferreira ^{[1
]}

Maciel-Rezende, Claudia Mara ^{[2
]}

Jesus, Larissa de Oliveira Passos ^{[3
]}

Pires, Francieli Ribeiro ^{[2
]}

Viegas Junior, Claudio ^{[2
]}

Izidoro, Mario Augusto ^{[4
]}

de Souza Judice, Wagner Alves ^{[3
]}

dos Santos, Marcelo Henrique ^{[2
]}

Marques, Marcos Jose ^{[1
]}

机构：

[1] Univ Fed Alfenas, Inst Ciencias Biomed, Lab Biol Mol Microorganismos, BR-37130000 Alfenas, MG, Brazil

[2] Univ Fed Alfenas, Inst Quim, Lab Fitoquim & Quim Med, BR-37130000 Alfenas, MG, Brazil

[3] Univ Mogi das Cruzes, Ctr Interdisciplinar Invest Bioquim, BR-08780911 Mogi Das Cruzes, SP, Brazil

[4] Univ Sao Paulo, Dept Microbiol Imunol & Parasitol, Lab Biol Celular Parasitas, BR-04039032 Sao Paulo, SP, Brazil

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2015年 / 75卷

关键词：

Leishmania amazonensis; Benzophenone derivatives; Cysteine proteases; GARCINIA-BRASILIENSIS; TRYPANOSOMA-CRUZI; MEXICANA; PROTEINASES; VIRULENCE; CPB; SPECIFICITIES; PEPTIDASES; EXPRESSION; AUTOPHAGY;

D O I：

10.1016/j.biopha.2015.08.030

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The leishmanicidal potential of benzophenones has been described, some of them highlighting their potential as cysteine protease inhibitors. Therefore, this work described leishmanicidal activity of nine benzophenone derivatives (1a-c; 2a-c; 3a-c) against intramacrophage amastigote forms of Leishmania (L.) amazonensis (IC50) and the cytotoxic effect on murine peritoneal macrophages (CC50). The derivative 1c exhibited a selectivity index SI (CC50/IC50) of 6.7, besides cytotoxicity lower than Amphotericin B (p < 0.05). Moreover it showed inhibitory activity against papain (42.8 +/- 0.3, p < 0.05), and when tested on trypanosomatids cysteine proteases 1c also proved to be a potent inhibitor of rCPB2.8, rCPB3.0 and cruzain, showing non-competitive inhibition mechanism by enzymatic assays in vitro. So, benzophenone 1c is interesting drug candidate prototype, with a multi-target directed mode of action, inhibiting rCPB2.8, rCPB3.0 and cruzain. (C) 2015 Elsevier Masson SAS. All rights reserved.

引用

页码：93 / 99

页数：7

共 34 条

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