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Apoptosis

, Volume 23, Issue 1, pp 27–40 | Cite as

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

  • Mohamad Norisham Mohamad Rosdi
  • Shahkila Mohd Arif
  • Mohamad Hafizi Abu Bakar
  • Siti Aisyah Razali
  • Razauden Mohamed Zulkifli
  • Harisun Ya’akob
Original Paper
  • 1k Downloads

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.

Keywords

Apoptosis Bcl-2 inhibitor Antiapoptotic proteins Annona muricata Linn Molecular docking MD simulation 

Notes

Acknowledgements

We deeply thank Dr Muhammad Helmi Nadri from Innovation Centre in Agritechnology for Advanced Bioprocessing, Universiti Teknologi Malaysia (UTM-ICA) for valuable comments and suggestions. This work was financially supported by Universiti Teknologi Malaysia and Ministry of Higher Education through Higher Institution Centres of Excellence (HICoE) research Grant (R.J130000.7846.4J261). MNMR was financially supported through Zamalah Scholarship, Universiti Teknologi Malaysia.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Mohamad Norisham Mohamad Rosdi
    • 1
  • Shahkila Mohd Arif
    • 2
  • Mohamad Hafizi Abu Bakar
    • 3
  • Siti Aisyah Razali
    • 4
  • Razauden Mohamed Zulkifli
    • 5
  • Harisun Ya’akob
    • 1
    • 6
  1. 1.Department of Bioprocess and Polymer Engineering, Faculty of Chemical and Energy EngineeringUniversiti Teknologi MalaysiaSkudaiMalaysia
  2. 2.Department of Biotechnology and Medical Engineering, Faculty of Biosciences and Medical EngineeringUniversiti Teknologi MalaysiaSkudaiMalaysia
  3. 3.Bioprocess Technology Division, School of Industrial TechnologyUniversiti Sains MalaysiaGelugorMalaysia
  4. 4.Bioinformatics Research Group, Faculty of Biosciences and Medical EngineeringUniversiti Teknologi MalaysiaSkudaiMalaysia
  5. 5.Department of Bioscience and Health Sciences, Faculty of Biosciences and Medical EngineeringUniversiti Teknologi MalaysiaSkudaiMalaysia
  6. 6.Institute of Bioproduct DevelopmentUniversiti Teknologi MalaysiaSkudaiMalaysia

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