Synthesis and antitumor activity of 6- and 2-(1-substituted-thio-4-methylpent-3-enyl)-5,8-dimethoxynaphthalene-1,4-diones

In an attempt to develop potent and selective antitumor agents, a series of 6- and 2-(1-substituted-thio-4-methylpent-3-enyl)-5,8-dimethoxynaphthalene-1,4-diones were designed and synthesized. The cytotoxicities of these compounds were evaluated in vitro against BEL-7402, HT-29 and SPC-A1 cell lines. The pharmacological results showed that most of the prepared compounds displayed the excellent selective cytotoxicity toward HT-29 cells. From the structure–activity relationships we may conclude that the introduction of a thioether functional group at the 1′-position in the side chain of shikonin is associated with an increase in cytotoxicity.

Graphical abstract The synthesis, biological evaluation and structure–activity relationships of 6- and 2-(1-substituted-thiol-4-methylpent-3-enyl)-5,8-dimethoxynaphthalene-1,4-diones as antitumor agents are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide