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

Abstract 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.