Natural polyphenolic inhibitors against the antiapoptotic BCL-2. (4th July 2017)

• Record Type: Journal Article
• Authors: Verma, Sharad; Singh, Aditi; Kumari, Anchala; Tyagi, Chetna; Goyal, Sukriti; Jamal, Salma; Grover, Abhinav
• Is Part Of: Journal of receptor and signal transduction research. Volume 37:Number 4(2017)
• Page Start: 391
• Page End: 400
• Publication Date: 2017-07-04
• Subjects: BCL-2 -- polyphenols -- molecular docking -- molecular dynamics simulation -- free energy calculation -- principal component analysis; Cell receptors -- Periodicals; Cellular signal transduction -- Periodicals; 571.6
• DOI: 10.1080/10799893.2017.1298129
• Languages: English
• ISSNs: 1079-9893

Abstract

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.