Synthesis, Anticancer Evaluation and Structure–Activity Relationship of Taiwanin a Derivatives

Abstract

Taiwanin A, a natural naphthalide lignan isolated from the heartwoods of Taiwania cryptomerioides Hayata, has previously been reported to have cytotoxicity against human tumor cells. In this study, a series of taiwanin A derivatives were synthesized and evaluated for their structure–activity relationship. Among the eleven taiwanin A derivatives, four compounds showed higher in vitro cytotoxic activity than taiwanin A. The biological evaluation of the synthesized compounds illustrated that the introduction of an electron-donating group in aryl ring A contributed to the antiproliferative potency, while in aryl ring B, it attenuated the cytotoxic activity. Compound 20 demonstrated excellent anticancer activity with an IC₅₀ value of 0.5 μM against HONE-1 human carcinoma cell lines, indicating that it could be a promising lead compound for further drug development studies.