Exploring of drug leads from diversity-oriented Michael-acceptor library derived from natural products
2012
Deng, Xu | Kong, Ling-Mei | Zhao, Yu | He, Juan | Peng, Li-Yan | Li, Yan | Zhao, Qin-Shi
A potential strategy for drug lead identification and in-active natural products re-discovery is elaborated. Starting from fifteen structurally diverse natural products, a focused library featured by Michael acceptors is constructed with IBX mediated oxidation. Biological assay on five tumor cell lines indicates that four Michael acceptors, 8a, 11a, 12a, 14a, are with improved cytotoxicity (3–10 folds more potent than the parent compounds), which merit further investigations. Further thiol-sensitive assay of the active hit 8a revealed that it was an irreversible Michael acceptor. The results suggest that the strategy is not only effective and relatively high discovery rate (28%), but also resource saving.
显示更多 [+] 显示较少 [-]