Interaction studies to evaluate 2- carboxyphenolate analogues as inhibitor of anti-apoptotic protein Bcl-2

Apoptosis is a cellular process that leads to the death of damaged cells. Its malfunction can cause cancer and poor response toconventional chemotherapy. After being activated by cellular stress signals, pro-apoptotic proteins bind anti-apoptotic proteins,thus allowing apoptosis to go forward. An excess of anti-apoptotic proteins can prevent apoptosis. Designed molecules that imitatethe roles of pro-apoptotic proteins can promote the death of cancer cells. In this work we have applied an insilico approach to studythe binding of 2-carboxyphenolate analogues as potent inhibitors of anti-apoptotic protein Bcl-2. Molecular docking study wasperformed in order to find specific binding mode using AutoDock. From the docking results it was observed that zinc 2-carboxyphenolate showed strong inhibition with Bcl-2 with docking energy of -4.6 kcal/mol. The effects of the Zinc 2-hydroxybenzoate on apoptosis in HT-1080 cell lines were also analysed, which shows strong evidence for their apoptotic mode ofaction using flow cytometric analysis of Annexin-V. Our study gave valuable insights on inhibitor specificity of anti-apoptoticproteins and might be considered as potent chemopreventive agents.