Natural polyphenolic inhibitors against the antiapoptotic BCL-2

Abstract

The apoptotic mechanism is regulated by the BCL-2 family of proteins, such as BCL-2 or Bcl-xL, which block apoptosis while Bad, Bak, Bax, Bid, Bim or Hrk induce apoptosis. The overexpression of BCL-2 was found to be related to the progression of cancer and also providing resistance towards chemotherapeutic treatments. In the present study, we found that all polyphenols (apigenin, fisetin, galangin and luteolin) bind to the hydrophobic groove of BCL-2 and the interaction is stable throughout MD simulation run. Luteolin was found to bind with highest negative binding energy and thus, claimed highest potency towards BCL-2 inhibition followed by fisetin. The hydrophobic interactions were found to be critical for stable complex formation as revealed by the vdW energy and ligplot analysis. Finally, on the basis of data obtained during the study, it can be concluded that these polyphenols have the potential to be used as lead molecules for BCL-2 inhibition.

Keywords:

• BCL-2
• polyphenols
• molecular docking
• molecular dynamics simulation
• free energy calculation
• principal component analysis

Acknowledgements

AG is grateful to University Grants Commission, India for the Faculty Recharge Position. SV is thankful of Council of Scientific and Industrial Research (CSIR), India, for providing senior research associateship (pool scientist scheme).

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.