TITLE:
Design and Molecular Docking Study of Antimycin A3 Analogues as Inhibitors of Anti-Apoptotic Bcl-2 of Breast Cancer
AUTHORS:
Ade Arsianti, Fadilah, Kusmardi, Hiroki Tanimoto, Tsumoru Morimoto, Kiyomi Kakiuchi
KEYWORDS:
Design, Docking, Antimycin A3, Analogue, Bcl-2, Breast Cancer
JOURNAL NAME:
Open Journal of Medicinal Chemistry,
Vol.4 No.3,
September
23,
2014
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.