Design and total synthesis of Mannich derivatives of marine natural product lamellarin D as cytotoxic agents

作者：Shen, Li; Xie, Nan; Yang, Bo; Hu, Yongzhou^*; Zhang, Yongmin

来源：European Journal of Medicinal Chemistry, 2014, 85: 807-817.

DOI：10.1016/j.ejmech.2014.08.038

• Lamellarin D
• Mannich
• Derivative
• Anti-cancer
• Topo I
• Structure-activity relationships

Enlightened by the modification route from Camptothecin (CPT) to Topotecan and based on classical drug design theory, a series of Mannich derivatives of lamellarin D were designed and synthesized in 26-27 steps starting from vanillin and isovanilin. All synthesized compounds were then biologically evaluated for their in vitro anti-cancer activities and Topo I inhibitory activities. The results showed that most target compounds exhibited Topo I inhibitory activities in equivalent level with that of lamellarin D. Compound SL-9 exhibited better Topo I inhibitory activity than that of lamellarin D. Compounds SL-2, SL-3, SL-4, SL-5 and SL-11 exhibited better anti-proliferative activity against HT-29 cells than that of lamellarin D.

• 出版日期2014-10-6
• 单位浙江大学