The natural flavone fukugetin as a mixed-type inhibitor for human tissue kallikreins

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:26

Article

Santos, Jorge A. N.¹  Kondo, Marcia Y.²  Freitas, Renato F.³  dos Santos, Marcelo H.⁴  Ramalho, Teodorico C.⁵  Assis, Diego M.²  Juliano, Luiz²  Juliano, Maria A.²  Puzer, Luciano⁶ 

[1] Inst Fed Ciencia Tecnol & Educ Sul Minas Gerais, Belo Horizonte, MG, Brazil

[2] Univ Fed Sao Paulo, Dept Biofis, Sao Paulo, SP, Brazil

[3] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA

[4] Univ Fed Vicosa, Dept Quim, Vicosa, MG, Brazil

[5] Univ Fed Lavras, Dept Quim, Lavras, MG, Brazil

[6] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09606070 Sao Bernardo Do Campo, SP, Brazil

关键词: Enzyme;    Serine protease;    Kallikrein;    Inhibitor;    Flavone;    Molecular docking;    Molecular dynamic simulation;   

DOI  :  10.1016/j.bmcl.2016.01.039

来源: Elsevier

【 摘 要 】

The human tissue kallikreins (KLK1-KLK15) comprise a family of 15 serine peptidases detected in almost every tissue of the human body and that actively participate in many physiological and pathological events. Some kallikreins are involved in diseases for which no effective therapy is available, as for example, epithelial disorders, bacterial infections and in certain cancers metastatic processes. In recent years our group have made efforts to find inhibitors for all kallikreins, based on natural products and synthetic molecules, and all the inhibitors developed by our group presented a competitive mechanism of inhibition. Here we describe fukugetin, a natural product that presents a mixed-type mechanism of inhibition against KLK1 and KLK2. This type of inhibitor is gaining importance today, especially for the development of exosite-type inhibitors, which present potential to selectively inhibit the enzyme activity only against specific substrate. (C) 2016 Elsevier Ltd. All rights reserved.

【 授权许可】

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