Design and Molecular Docking Study of Antimycin A<sub>3</sub>Analogues as Inhibitors of Anti-Apoptotic Bcl-2 of Breast Cancer

• 作者: Fadilah Kusmardi Ade Arsianti Hiroki Tanimoto Kiyomi Kakiuchi Tsumoru Morimoto
• 来源期刊: 药物化学期刊(英文)
• 学科: 医学
• 关键词: DESIGN Docking ANTIMYCIN A3 Analogue BCL-2 Breast Cancer
• 年，卷（期）: 2014,（3）
• 页码范围: 79-86
• 页数: 8页
• 分类号: R73

摘要

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.