Planta Med 2008; 74 - PC150
DOI: 10.1055/s-0028-1084668

Search for Protease-inhibiting compounds from Cerrado and Atlantic plant species

VS Bolzani 1, OJ Flausino 1, JMJ Batista 1, AA Lopes 1, W Altei 1, M Furlan 1, I Castro-Gamboa 1, DHS Silva 1
  • 1Nuclei of Bioassays, Biosynthesis and Ecophysiology of Natural Products – NuBBE, São Paulo State University – UNESP – Chemistry Institute, Department of Organic Chemistry, Rua Prof. Francisco Degni s/n –14.800–900– Araraquara – São Paulo – Brazil

Modulation of protease activity with synthetic derived inhibitors has proven to be clinically useful for treating HIV and hypertension, and has shown potential for medicinal application in cancer, obesity, cardiovascular, neurodegenerative diseases, and various infectious and parasitic diseases. Recently, several natural compounds have provided to be promising inhibitors in animal studies [1]. In a search for bioactive compounds from tropical and subtropical biomes, we evaluated the inhibitory activity of compounds isolated from plant species of Cerrado and Atlantic forest using a fluorescent protease assay. Subtilisin Carlsberg (37 nM) and a fluorescent HIV substrate (2µM) were used as a tool for this screening evaluation, performed in a solution of 0.1M phosphate buffer (pH 7.5) with 0.1M NaCl2 (Sigma-Aldrich). Fluorescence (355nm excitation and 460nm emission filters during 1 hr) were measured with SynergyTM Microplate Reader (BioTek Instruments) and KC4TM software. After preliminary screening with various secondary metabolites, two chromenes 1-2 isolated from Piper aduncum and a new cyclic peptide 3 isolated from Jatropha curcas showed moderate inhibitory activity, when compared with standard assay (without inhibitor).

Acknowledgements: FAPESP, CAPES and CNPq for financial support.

References: 1. Fear et al. (2007) Pharmacol. Therap. 113: 354.

2. Davis et al. (2006) Antiviral Res. 72: 89.