Inhibition of cysteine proteases by a natural biflavone: behavioral evaluation of fukugetin as papain and cruzain inhibitor

Inhibition of cysteine proteases by a natural biflavone: behavioral evaluation of fukugetin as papain and cruzain inhibitor

Author Assis, Diego Magno Autor UNIFESP Google Scholar
Gontijo, Vanessa Silva Google Scholar
Pereira, Ivan de Oliveira Google Scholar
Nogueira Santos, Jorge Alexandre Autor UNIFESP Google Scholar
Camps, Ihosvany Google Scholar
Nagem, Tanus Jorge Google Scholar
Ellena, Javier Google Scholar
Izidoro, Mario Augusto Autor UNIFESP Google Scholar
Santos Tersariol, Ivarne Luis dos Autor UNIFESP Google Scholar
Tenorio de Barros, Nilana Meza Autor UNIFESP Google Scholar
Doriguetto, Antonio Carlos Google Scholar
Santos, Marcelo Henrique dos Google Scholar
Juliano, Maria Aparecida Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Univ Fed Alfenas
Univ Fed Ouro Preto
Universidade de São Paulo (USP)
Abstract Cruzain is the major cysteine protease of Trypanosoma cruzi, the infectious agent responsible for Chagas disease, and cruzain inhibitors display considerable antitrypanosomal activity. in the present work we elucidated crystallographic data of fukugetin, a biflavone isolated from Garcinia brasiliensis, and investigated the role of this molecule as cysteine protease inhibitor. the kinetic analyses demonstrated that fukugetin inhibited cruzain and papain by a slow reversible type inhibition with K-I of 1.1 and 13.4 mu M, respectively. However, cruzain inhibition was about 12 times faster than papain inhibition. Lineweaver-Burk plots demonstrated partial competitive inhibition for cruzain and hyperbolic mixed-type inhibition for papain. Furthermore, the docking results showed that the biflavone binds to ring C' in the S2 pocket and to ring C in the S3 pocket through hydrophobic interactions and hydrogen bonds. Finally, fukugetin also presented inhibitory activity on proteases of the T. cruzi extract, with IC50 of 7 mu M.
Keywords Biflavones
protease inhibition
molecular docking
cysteine proteases
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)
Grant number 08/54894-4
Date 2013-08-01
Published in Journal of Enzyme Inhibition and Medicinal Chemistry. London: Informa Healthcare, v. 28, n. 4, p. 661-670, 2013.
ISSN 1475-6366 (Sherpa/Romeo, impact factor)
Publisher Informa Healthcare
Extent 661-670
Access rights Closed access
Type Article
Web of Science ID WOS:000321693400002

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