Synthesis and antitumor activity of nitrogen-based thiocolchicine derivatives.

To search for colchicine derivatives which have high efficacy and low toxicity. Colchicine was firstly converted into thiocolchicine, and then it was hydrolyzed to get 7-(N-deacetylthiocolchicine). At last, 7-(N-deacetylthiocolchicine) was amidated to get the target compounds. The chemical structure of these new derivatives was confirmed with 1H NMR, IR, MS, and HR-MS. The cytotoxicity of the compounds was tested by MTT assay. Their in vivo antitumor activity was evaluated against mice tumor H22 and U14. Twelve thiocolchicine derivatives are new compounds. In vitro antitumor activity has showed that some of these thiocolchicines possessed cytotoxic activity superior to colchicine. However, in vivo antitumor activity indicated that these derivatives have poor efficacy in mice.