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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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Assis, Diego Magno [1] ; Gontijo, Vanessa Silva [2] ; Pereira, Ivan de Oliveira [2] ; Nogueira Santos, Jorge Alexandre [1] ; Camps, Ihosvany [2] ; Nagem, Tanus Jorge [3] ; Ellena, Javier [4] ; Izidoro, Mario Augusto [1] ; dos Santos Tersariol, Ivarne Luis [5] ; Tenorio de Barros, Nilana Meza [1] ; Doriguetto, Antonio Carlos [2] ; dos Santos, Marcelo Henrique [2] ; Juliano, Maria Aparecida [1]
Total Authors: 13
Affiliation:
[1] Univ Fed Sao Paulo, Dept Biophys, Sao Paulo - Brazil
[2] Univ Fed Alfenas, Inst Exact Sci, Alfenas, MG - Brazil
[3] Univ Fed Ouro Preto, ICEB LAPRONA, Ouro Preto, MG - Brazil
[4] Univ Sao Paulo, Inst Phys, Dept Phys & Informat, Sao Carlos, SP - Brazil
[5] Univ Fed Sao Paulo, Dept Biochem, Sao Paulo - Brazil
Total Affiliations: 5
Document type: Journal article
Source: Journal of Enzyme Inhibition and Medicinal Chemistry; v. 28, n. 4, p. 661-670, AUG 2013.
Web of Science Citations: 11
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. (AU)