6100-60-3Relevant articles and documents
Design, Synthesis and Structure-Activity Relationship Studies of Glycosylated Derivatives of Marine Natural Product Lamellarin D
Zheng, Liuliu,Gao, Tingting,Ge, Zhiwei,Ma, Zhongjun,Xu, Jinzhong,Ding, Wanjing,Shen, Li
, (2021/02/16)
Lamellarin D, a marine natural product, acts as a potent inhibitor of DNA topoisomerase I (Topo I). To modify its physicochemical property and biological activity, a series of mono- and di-glycosylated derivatives were designed and synthesized through 22–26 multi-steps. Their inhibition of human Topo I was evaluated, and most of the glycosylated derivatives exhibited high potency in inhibiting Topo I activity as well as lamellarin D. All the 15 target compounds were evaluated for their cytotoxic activities against five human cancer cell lines. The typical lamellarin derivative ZL?3 exhibited the best activity with IC50 values of 3 nM, 10 nM, and 15 nM against human lung cancer A549 cells, human colon cancer HCT116 cells and human hepatocellular carcinoma HepG2 cells. Compound ZL?1 exhibited anti-cancer activity with IC50 of 14 nM and 24 nM against human colon cancer HCT116 cells and human hepatocellular carcinoma HepG2 cells, respectively. Cell cycle analysis in MDA-MB-231 suggested ZL?3 inhibited cell growth through arresting cells at the G2/M phase of the cell cycle. Further tests showed a significant improvement in aqueous solubility of ZL?1 and ZL?7. This study suggested that glycosylation could be utilized as a useful strategy to optimize lamellarin D derivatives as Topo I inhibitors and anticancer agents.
Kolbe-Schmitt type reaction under ambient conditions mediated by an organic base
Sadamitsu, Yuta,Okumura, Akira,Saito, Kodai,Yamada, Tohru
supporting information, p. 9837 - 9840 (2019/08/20)
The combined use of an organic base for resorcinols realized a Kolbe-Schmitt type reaction under ambient conditions. When resorcinols (3-hydroxyphenol derivatives) were treated with DBU under a carbon dioxide atmosphere, nucleophilic addition to carbon dioxide proceeded to afford the corresponding salicylic acid derivatives in high yields.
Design and total synthesis of Mannich derivatives of marine natural product lamellarin D as cytotoxic agents
Shen, Li,Xie, Nan,Yang, Bo,Hu, Yongzhou,Zhang, Yongmin
, p. 807 - 817 (2014/10/15)
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.
