Semi-synthesis and antitumor activity of 6-isomers of 5, 8-O-dimethyl acylshikonin derivatives

We recently discovered that 5, 8-O-dimethyl acylshikonin derivatives displayed the selectivity towards MCF-7 and no toxicity to normal cells. Herein, a series of the corresponding 6-isomers of 5, 8-O-dimethyl acylshikonin derivatives were synthesized starting from shikonin. In vitro evidence of the cytotoxicities indicated that most of thecompounds were more active than or comparative to shikonin and retained the selectivity against MCF-7, MDA-MB-231 besides no toxicity in the normal cells. Also, in vivo anticancer activity of the positional isomers 5p, 6c further showed that 6-isomers of 5, 8-O-dimethyl acylshikonin derivatives were more active than their corresponding 2-isomers. Thus, we may conclude that the position of the side chain of shikonin attached to 5,8-dimethoxy -1,4-naphthoquinone is associated with the antitumor activity.

A series of the 6-isomers of 5, 8-O-dimethyl acylshikonin derivatives were synthesized and evaluated for their cytotoxicities. The in vivo antitumor activities of two corresponding isomers were also compared.Figure optionsDownload as PowerPoint slideHighlights
► The 6-isomers of 5, 8-O-dimethyl acylshikonin derivatives were synthesized.
► Their activities of several pairs of isomers to cancer cells were investigated.
► Twenty-two derivatives against two breast cancer cells were further assessed.
► The in vivo antitumor activities of a pair of isomers were evaluated.
► The derivatives displayed the higher selectivity and lower toxicity.