Exploring of drug leads from diversity-oriented Michael-acceptor library derived from natural products

doi:10.1007/s13659-012-0071-7

Natural Products and Bioprospecting ›› 2012, Vol. 2 ›› Issue (5): 210-216.DOI: 10.1007/s13659-012-0071-7

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Exploring of drug leads from diversity-oriented Michael-acceptor library derived from natural products

Xu DENG^a,b, Ling-Mei KONG^a,b, Yu ZHAO^a, Juan HE^a, Li-Yan PENG^a, Yan LI^a, Qin-Shi ZHAO^a

a State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China;
b Graduate University of Chinese Academy of Sciences, Beijing 100049, China

Received:2012-08-19 Revised:2012-09-12 Online:2018-02-11 Published:2012-10-24
Supported by:
We thanked the National Natural Science Foundation of China(No. 90813004, U0932602, 20802083 and 973 Program No. 2009CB522303 and No. 2011CB915503) and the State Key Laboratory of Phytochemistry and Plant Resources in West China(P2010-ZZ18) for financial support.

Exploring of drug leads from diversity-oriented Michael-acceptor library derived from natural products

Xu DENG^a,b, Ling-Mei KONG^a,b, Yu ZHAO^a, Juan HE^a, Li-Yan PENG^a, Yan LI^a, Qin-Shi ZHAO^a

a State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China;
b Graduate University of Chinese Academy of Sciences, Beijing 100049, China

通讯作者: Yan LI,E-mail:liyanb@mail.kib.ac.cn;Qin-Shi ZHAO,E-mail:qinshizhao@mail.kib.ac.cn
基金资助:
We thanked the National Natural Science Foundation of China(No. 90813004, U0932602, 20802083 and 973 Program No. 2009CB522303 and No. 2011CB915503) and the State Key Laboratory of Phytochemistry and Plant Resources in West China(P2010-ZZ18) for financial support.

Abstract

Abstract: 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.

Key words: drug leads identification, in-active natural products re-discovery, Michael acceptors, anti-tumor activity

摘要： 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.

关键词: drug leads identification, in-active natural products re-discovery, Michael acceptors, anti-tumor activity

Xu DENG, Ling-Mei KONG, Yu ZHAO, Juan HE, Li-Yan PENG, Yan LI, Qin-Shi ZHAO. Exploring of drug leads from diversity-oriented Michael-acceptor library derived from natural products[J]. Natural Products and Bioprospecting, 2012, 2(5): 210-216.

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Exploring of drug leads from diversity-oriented Michael-acceptor library derived from natural products

Exploring of drug leads from diversity-oriented Michael-acceptor library derived from natural products

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