4′-Hydroxy-6,7-methylenedioxy-3-methoxyflavone: A novel flavonoid from Dulacia egleri with potential inhibitory activity against cathepsins B and L

被引：10

作者：

de Novais, Leice M. R. ^{[1
]}

de Arueira, Cauane C. O. ^{[1
]}

Ferreira, Luiz F. ^{[1
]}

Ribeiro, Tereza A. N. ^{[1
]}

Sousa, Paulo T., Jr. ^{[1
]}

Jacinto, Marcos J. ^{[1
]}

de Carvalho, Mario G. ^{[2
]}

Judice, Wagner A. S. ^{[3
]}

Jesus, Larissa O. P. ^{[3
]}

de Souza, Aline A. ^{[3
]}

Torquato, Heron F. V. ^{[4
]}

Paredes-Gamero, Edgar J. ^{[3
]}

Silva, Virginia C. ^{[1
]}

机构：

[1] Univ Fed Mato Grosso, Dept Quim, Cuiaba, MT, Brazil

[2] Univ Fed Rural Rio de Janeiro, Dept Quim, Seropedica, RJ, Brazil

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

[4] Univ Fed Sao Paulo, Dept Bioquim, Campus Sao Paulo, Sao Paulo, Brazil

来源：

FITOTERAPIA | 2019年 / 132卷

基金：

巴西圣保罗研究基金会;

关键词：

Dulacia egleri; Flavonoid; Nucleosides; Cathepsin inhibition; Cooperativity inhibition; X-RAY-ANALYSIS; GUIANENSIS; RIBAVIRIN; PROTEASES; ENZYMES;

D O I：

10.1016/j.fitote.2018.08.005

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new flavone, 4'-hydroxy-6,7-methylenedioxy-3-methoxyflavone 1, and two other nucleosides, ribavirin 2 and adenosine 3, were isolated from the leaves of Dulacia egleri. The nucleosides were identified by spectroscopic techniques (1D, 2D-NMR) while the structure of the flavonoid was established by 1D, 2D-NMR analysis, including HRESIMS data. The results obtained in the biological assays showed that the compound 1 was able to inhibit cathepsins B and L with IC50 of 14.88 +/- 0.18 mu M and 3.19 +/- 0.07 mu M, respectively. The mechanism of inhibition for both enzymes were determined showing to be competitive at cathepsin B with Ki = 12.8 +/- 0.6 mu M and non-linear non-competitive with positive cooperativity inhibition at cathepsin L with K-i = 322 +/- 33 mu M, alpha K-i= 133 +/- 15 mu M, beta K-i = 5.14 +/- 0.41 mu M and gamma K-i = 13.2 +/- 13 mu M.

引用

页码：26 / 29

页数：4

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