Design, synthesis and anticancer activity evaluation of novel C14 heterocycle substituted epi-triptolide

• Synthesis of novel C14-aryl heterocycle substituted epi-triptolide analogs.
• In vitro antitumor activity evaluation.
• Compounds with triazolylmethyl substituents proved to be inactive.
• Compounds with aryl heterocycle aminomethyl substituents showed potent cytotoxity.
• The structure–activity relationship of triptolide analogs were summarized.

Two series of novel C14 heterocycle substituted epi-triptolide derivatives as potential anticancer agents were synthesized and tested for their cytotoxicity against SKOV-3 and PC-3 tumor cell lines. The introduction of C14β-aryl heterocycle aminomethyl substituent to the leading compound was found to be an effective modification method to retain the potent anticancer activity. Meanwhile, the series of epi-triptolide derivatives (21–40) with C14α-hydroxyl group, still retained the natural product's cytotoxicity. This is apparently challenges the classical structure–activity relationship of triptolide that considers the C14β-hydroxyl group to be essential for its anticancer activity.

Figure optionsDownload as PowerPoint slide