Insilico Analysis of Plumbagin and its synthetic analogues as potential Bcl-2 Inhibitors

Alexander Ronaldo Anuf*, BreethiNatarajan, Shahila Stephen and KannanRamaraj
Department of Biotechnology, Kamaraj College of Engineering and Technology, Virudhunagar
NCADDD, 25 July 2014, Organized by Department of Pharmaceutical Technology, Anna University, BIT Campus, Tiruchirappalli–620024, Tamil Nadu, India

Abstract
Plumbagin (5-hydroxy-2-methyl-1,4-napthoquinone), a quinonoid constituent isolated from roots of different Plumbaginales namely, Plumbago rosea, P.zeylanica, P.capensis, P.capensis. Potential role of Plumbagin as an anticancer effects have been reported in diverse cancer models such as prostate, lung, cervical, ovarian as well as melanoma. A recent report has showed that plumbagin induced cell cycle arrest and apoptosis in human melanoma cells by inhibition of Bcl-2 over expression. Bcl-2 is one of the most important proteins implicated in inhibition of apoptosis. Functional blockage of the above protein could restore the apoptotic pathway in tumor cells.In present study six different synthetic analogues of Plumbagin were analyzed for its activity against anti-apoptotic protein, Bcl-2. Molecular docking analysis using the Schrödinger Maestro software revealed benzoate plumbagin (CID: 46835862) showed more potent inhibitory activity against Bcl-2 protein, with a maximum interaction energy of -34.29 kcal/mol compared to that of plumbagin -23.39 Kcal/mol. The mode of interaction of all the six analogues was much stronger in contrast with standard plumbagin. This study provides new insights in understanding the six different analogues as potential candidates for cancer therapy.
Keywords: Bcl-2, Plumbagin, Glide, Epik