Back to Journals » Drug Design, Development and Therapy » Volume 10

Acetogenins from Annona muricata as potential inhibitors of antiapoptotic proteins: a molecular modeling study

Authors Antony P, Vijayan R

Received 27 December 2015

Accepted for publication 16 February 2016

Published 13 April 2016 Volume 2016:10 Pages 1399—1410

DOI https://doi.org/10.2147/DDDT.S103216

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Lucy Goodman

Peer reviewer comments 5

Editor who approved publication: Prof. Dr. Wei Duan


Priya Antony, Ranjit Vijayan

Department of Biology, College of Science, United Arab Emirates University, Al Ain, Abu Dhabi, United Arab Emirates

Abstract: Apoptosis is a highly regulated process crucial for maintaining cellular homeostasis and development. The B-cell lymphoma 2 (Bcl-2) family of proteins play a crucial role in regulating apoptosis. Overexpressed Bcl-2 proteins are associated with the development and progression of several human cancers. Annona muricata is a tropical plant that belongs to the Annonaceae family and is well known for its anticancer properties. In this study, molecular docking and simulations were performed to investigate the inhibitory potential of phytochemicals present in A. muricata against antiapoptotic proteins of the Bcl-2 family including Bcl-2, B-cell lymphoma extra-large (Bcl-Xl), and Mcl-1. Docking results revealed that the acetogenins, such as annomuricin A, annohexocin, muricatocin A, annomuricin-D-one, and muricatetrocin A/B, exhibited strong binding interactions with Bcl-Xl when compared to Bcl-2 and Mcl-1. Binding score and interactions of these acetogenins were notably better than those of currently available synthetic and natural inhibitors. Molecular dynamics simulations of the top-scoring lead molecules established that these molecules could bind strongly and consistently in the active site of Bcl-Xl. These results suggest that acetogenins could be explored as selective natural inhibitors of Bcl-Xl that could assist in promoting the intrinsic pathway of apoptosis.

Keywords: apoptosis, molecular docking, molecular dynamics, phytocompounds, drug discovery

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]