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Bioorg Med Chem Lett. 2016 Mar 1;26(5):1485-9. doi: 10.1016/j.bmcl.2016.01.039. Epub 2016 Jan 23.

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

Author information

1
Instituto Federal de Ciência, Tecnologia e Educação do Sul de Minas Gerais, Campus Inconfidentes, MG, Brazil.
2
Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
3
Department of Biology, The Johns Hopkins University, Baltimore, MD, USA.
4
Departamento de química, Universidade Federal de Viçosa, Viçosa, MG, Brazil.
5
Departamento de química, Universidade Federal de Lavras, Lavras, MG, Brazil.
6
Centro de Ciências Naturais e Humanas, Bloco Delta, Sala 210, Universidade Federal do ABC, Rua Arcturus 3, São Bernardo do Campo, SP 09606-070, Brazil. Electronic address: luciano.puzer@ufabc.edu.br.

Abstract

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.

KEYWORDS:

Enzyme; Flavone; Inhibitor; Kallikrein; Molecular docking; Molecular dynamic simulation; Serine protease

PMID:
26848109
DOI:
10.1016/j.bmcl.2016.01.039
[Indexed for MEDLINE]

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