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Spiramine derivatives induce apoptosis of Bax(-/-)/Bak(-/-) cell and cancer cells

Bioorganic & Medicinal Chemistry Letters 24(8): 1884-1888
Spiramine derivatives induce apoptosis of Bax(-/-)/Bak(-/-) cell and cancer cells
Spiramine C-D, the atisine-type diterpenoid alkaloids isolated from the Chinese herbal medicine Spiraea japonica complex, are shown to have anti-inflammatory effects in vitro. In this study, we report that spiramine derivatives of spiramine C-D bearing α,β-unsaturated ketone induce apoptosis of Bax(-/-)/Bak(-/-) MEFs cell, which is positively corresponding their cytotoxicity of tumor cell lines including multidrug resistance MCF-7/ADR. The results indicated that oxazolidine ring is necessary, and derivatives bearing double 'Michael reaction acceptor' group would significantly increased activities both of inducing apoptosis of Bax(-/-)/Bak(-/-) cells and cytotoxicity of tumor cells. The result indicated that spiramine derivative with α,β-unsaturated ketone group is a new anti-cancer agent with a capability of inducing apoptosis of cancer cells in Bax/Bak-independent manner.

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Accession: 055884332

PMID: 24684844

DOI: 10.1016/j.bmcl.2014.03.019

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