Design and Molecular Docking Study of Antimycin A₃ Analogues as Inhibitors of Anti-Apoptotic Bcl-2 of Breast Cancer

Ade Arsianti^1*,   Fadilah¹,   Kusmardi², Hiroki Tanimoto³, Tsumoru Morimoto³, Kiyomi Kakiuchi³

¹Department of Medical Chemistry, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
²Department of Anatomical Pathology, Faculty of Medicine, University of Indonesia, Jakarta,Indonesia.
³Graduate School of Materials Science, Nara Institute of Science and Technology (NAIST), Nara, Japan.

DOI: 10.4236/ojmc.2014.43006                

Abstract

In this paper, we report the design and moleculardocking study of analogues of antimycin A₃ as inhibitors of anti-apoptotic Bcl-2 of breast cancer. Twenty designed compounds and the original antimycin A₃ were docked based on their interaction with breast tumor receptor binding target Bcl-2. The docking resulted in the five top-ranked compounds, namely, compounds 11, 14, 15, 16, and 20, which have a lower G binding energy, better affinity and stronger hydrogen bonding interactions to the active site of Bcl-2 than antimycin A₃. Among those five top-ranked compounds, analogue compounds 11 and 14, which have an 18-membered tetralactone core and 18-membered tetraol core, respectively, exhibited the strongest hydrogen bond interaction, formed high stability conformation, and demonstrated the greatest inhibitory activity on the catalytic site of Bcl-2.

Keywords

Design, Docking, Antimycin A₃, Analogue, Bcl-2, Breast Cancer

Conflicts of Interest

The authors declare no conflicts of interest.

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