Molecular docking studies of bioactive compounds from Annona muricata Linn as potential inhibitors for Bcl-2, Bcl-w and Mcl-1 antiapoptotic proteins

Abstract

Annona muricata Linn or usually identified as soursop is a potential anticancer plant that has been widely reported to contain valuable chemopreventive agents known as annonaceous acetogenins. The antiproliferative and anticancer activities of this tropical and subtropical plant have been demonstrated in cell culture and animal studies. A. muricata L. exerts inhibition against numerous types of cancer cells, involving multiple mechanism of actions such as apoptosis, a programmed cell death that are mainly regulated by Bcl-2 family of proteins. Nonetheless, the binding mode and the molecular interactions of the plant's bioactive constituents have not yet been unveiled for most of these mechanisms. In the current study, we aim to elucidate the binding interaction of ten bioactive phytochemicals of A. muricata L. to three Bcl-2 family of antiapoptotic proteins viz. Bcl-2, Bcl-w and Mcl-1 using an in silico molecular docking analysis software, Autodock 4.2. The stability of the complex with highest affinity was evaluated using MD simulation. We compared the docking analysis of these substances with pre-clinical Bcl-2 inhibitor namely obatoclax. The study identified the potential chemopreventive agent among the bioactive compounds. We also characterized the important interacting residues of protein targets which involve in the binding interaction. Results displayed that anonaine, a benzylisoquinoline alkaloid, showed a high affinity towards the Bcl-2, thus indicating that this compound is a potent inhibitor of the Bcl-2 antiapoptotic family of proteins.

Identification of Aloperine as an anti-apoptotic Bcl2 protein inhibitor in glioma cells

“…Riaz et al (2018) showed that astragalin functions include the regulation and modulation of various molecular targets, such as transcription factors, enzymes, kinases, cell adhesion proteins, inflammatory cytokines and apoptosis proteins (such as anti-apoptotic Bcl-2). Using molecular docking, several bioactive compounds from Annona muricata Linn were shown to be potential inhibitors of anti-apoptotic proteins, such as Bcl-2, Bcl-w and Mcl-1 (Mohamad Rosdi et al, 2018). In a structure-based virtual ligand screening, 8-chrysoeriol, a bioactive flavonoid, was identified to bind directly to Bcl-2, similar to BH3 mimetics, and to trigger apoptosis in pancreatic cancer cells (Zhang et al, 2018).…”

Molecular Docking Studies of Bioactive Compounds from Solenostemma Argel Leaf Extract as Potential Inhibitor for BCL-2 Antiapoptotic Proteins

“…Gold Gold = S (hb_ext) + S (vdw_ext) + S (hb_int) + S (vdw_int) Here in this equation S (hb_ext is protein-ligand hydrogen bond, S (vdw_ext) points for protein-ligand van der Waals, S (hb_int) stands for intramolecular hydrogen bond to ligand and S (vdw_int) is the intramolecular strain to the ligand [21].…”

Characterization and Investigation of Stigmasterol Isolated from Rodent Tuber Mutant Plant (<em>Typhonium flagelliforme</em>), Its Molecular Docking as Anticancer on MF-7 Cells

“…In silico methods, such as molecular docking, have been used to predict the molecular mechanism of bioactive compounds at the atomic level [14][15][16]. Therefore, in this work, we also explored the anti-breast cancer activity of the isolated compound using the molecular docking method.…”