title: Interaction studies to evaluate 2- carboxyphenolate analogues as inhibitor of anti-apoptotic protein Bcl-2.
abstract: Apoptosis is a cellular process that leads to the death of damaged cells. Its malfunction can cause cancer and poor response to conventional 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 imitate the roles of pro-apoptotic proteins can promote the death of cancer cells. In this work we have applied an insilico approach to study the binding of 2-carboxyphenolate analogues as potent inhibitors of anti-apoptotic protein Bcl-2. Molecular docking study was performed 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 of action using flow cytometric analysis of Annexin-V. Our study gave valuable insights on inhibitor specificity of anti-apoptotic proteins and might be considered as potent chemopreventive agents.
authors.affiliation: Dean of Faculty of Health Sciences, Buraydah Colleges, Al-Qassim - Buraydah, P.O.Box 51418.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Al-Karaawi
keywords: 2-carboxyphenolate analogues; 2-hydroxybenzoate analogues; Apoptosis; AutoDock; Bcl-2; Docking