Synthesis and structure–activity relationship studies of cytotoxic cinnamic alcohol derivatives

Abstract

Three series of di- and trisubstituted derivatives of cinnamic alcohol and its conjugated dienol analogues were designed and synthesised. The derivatives were screened for cytotoxicity against nine tumour cell lines: KB, A549, Hela, CNE, PC-3, BEL-7404, HL-60, BGC823 and P388D1. Most of the cinnamic alcohol derivatives showed cytotoxic activity. The compound 7-(4′,5′-dichlorobenzyloxy)-6,8-dihydroxycinnamic alcohol (55) exhibited significant cytotoxicity to seven human tumour cell lines on a micromolar range, especially with regard to the KB and P388D1 cell lines, showing IC₅₀ values of 0.4 and 0.5 µM, respectively. The structure–activity relationships of the derivatives are discussed.

Keywords:

• cinnamic alcohol derivatives
• cytotoxicity
• structure–activity relationship

Acknowledgements

This work was in part financially supported by the Special Foundation 985 from Zhejiang University, the German Science Foundation (Bad Godesberg) and Zhejiang University K.P. Chao's Foundation. The authors are grateful to Prof. Handong Sun and Prof. Jun Zhou (KIB, CAS), as well as to Françoise Guéritte (ICSN, CNRS) for their interest in this research topic. We thank Dr Jiali Luo and Mr Xiaoren Wang at the R&D Centre of Zhejiang Hisun Group for measuring the mass data.