Docking studies to evaluate mushrooms low molecular weight compounds as inhibitors of the anti-apoptotic protein BCL-2

Several reports indicate that mushrooms have the ability to promote apoptosis in tumour cell lines, but the mechanism of action is not quite well understood. Inhibition of the interaction between Bcl-2 (anti-apoptotic protein) and pro-apoptotic proteins could be an important step that leads to apoptosis. Therefore, the discovery of compounds with the capacity to inhibit Bcl-2 is an ongoing research topic on cancer therapy. Herein, Autodock4 virtual screening was applied to a dataset of 40 low molecular weight compounds present in mushrooms, using 3D Bcl-2 protein structure (PDB:2XA0) as target. Results suggested that steroids mainly ergosta-4,6,8(14),22-tetraen-3-one, lucidenic lactone, cerevisterol, ganoderic acid w and ganoderic acid x, with a binding energy lower than -10kcal/mol, had the ability to interact with Bcl-2.

Acknowledgements: FCT and COMPETE/QREN/EU- project PTDC/AGR-ALI/110062/2009, PEst-OE/AGR/UI0690/2011 (CIMO) and grant BPD/4609/2008 (L. Barros).