Inhibition of cysteine proteases by a natural biflavone: behavioral evaluation of fukugetin as papain and cruzain inhibitor. (August 2013)

• Record Type: Journal Article
• Authors: Assis, Diego Magno; Gontijo, Vanessa Silva; de Oliveira Pereira, Ivan; Santos, Jorge Alexandre Nogueira; Camps, Ihosvany; Nagem, Tanus Jorge; Ellena, Javier; Izidoro, Mario Augusto; dos Santos Tersariol, Ivarne Luis; de Barros, Nilana Meza Tenório; Doriguetto, Antonio Carlos; dos Santos, Marcelo Henrique; Juliano, Maria Aparecida
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 28:Number 4(2013:Aug.)
• Page Start: 661
• Page End: 670
• Publication Date: 2013-08
• Subjects: Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.3109/14756366.2012.668539
• Languages: English
• ISSNs: 1475-6366

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>Cruzain is the major cysteine protease of <italic>Trypanosoma cruzi</italic>, 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 <italic>Garcinia brasiliensis</italic>, 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 µM, 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 <italic>T. cruzi</italic> extract, with IC₅₀ of 7 µM.</p> </abstract>