Biological evaluation and docking studies of natural isocoumarins as inhibitors for human kallikrein 5 and 7

Biological evaluation and docking studies of natural isocoumarins as inhibitors for human kallikrein 5 and 7

Author Teixeira, Thiago S. P. Google Scholar
Freitas, Renato F. Google Scholar
Abrahao, Odonirio Google Scholar
Devienne, Karina F. Google Scholar
Souza, Lucas R. de Google Scholar
Blaber, Sachico I. Google Scholar
Blaber, Michael Google Scholar
Kondo, Marcia Y. Autor UNIFESP Google Scholar
Juliano, Maria A. Autor UNIFESP Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Puzer, Luciano Google Scholar
Institution Universidade Federal do ABC (UFABC)
Univ Fed Triangulo Mineiro
Florida State Univ
Universidade Federal de São Paulo (UNIFESP)
Abstract Human kallikrein 5 and 7 (KLK5 and KLK7) are trypsin-like and chymotrypsin-like serine proteases, respectively, and promising targets for the treatment of skin desquamation, inflammation and cancer. in an effort to develop new inhibitors for these enzymes, we carried out enzymatic inhibition assays and docking studies with three isocoumarin compounds. Some promising inhibitors were uncovered, with vioxanthin and 8,8'-paepalantine being the most potent competitive inhibitors of KLK5 (K(i) = 22.9 mu M) and KLK7 (K(i) = 12.2 mu M), respectively. Our docking studies showed a good correlation with the experimental results, and revealed a distinct binding mode for the inhibitors at the binding sites of KLK5 and KLK7. in addition, the docking results suggested that the formation of hydrogen bonds at the oxyanion hole is essential for a good inhibitor. (C) 2011 Elsevier B.V. All rights reserved.
Keywords Peptidases
Kallikreins
Protease inhibitors
Docking
Isocoumarins
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Grant number FAPESP: 06/53607-6
CNPq: 312701/2009-8
Date 2011-10-15
Published in Bioorganic & Medicinal Chemistry Letters. Oxford: Pergamon-Elsevier B.V., v. 21, n. 20, p. 6112-6115, 2011.
ISSN 0960-894X (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 6112-6115
Origin http://dx.doi.org/10.1016/j.bmcl.2011.08.044
Access rights Closed access
Type Article
Web of Science ID WOS:000295494500018
URI http://repositorio.unifesp.br/handle/11600/34147

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