Synthesis and antitumor activity of nitrogen-based thiocolchicine derivatives / 药学学报

Aim To search for colchicine derivatives which have high efficacy and low toxicity. Methods 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. Results Twelve thiocolchicine derivatives are new compounds. Conclusion 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.

Synthesis and antitumor activity of A-ring modified hexacyclic analogues of camptothecin / 药学学报

Aim To improve the biological activity of A-ring modified analogues of camptothecin.Methods A-ring modified camptothecins were synthesized from 10-hydroxycamptothecin or 7-ethyl-10-hydroxycamptothecin (SN-38) in three or four steps. Their cytotoxicity was evaluated using MTT assay,and their in vivo antitumor activity against mouse liver cancer H22 was tested. Results Five hexacyclic camptothecins (6a, 6b, 6c, 7a and 7b) are target compounds, and ten camptothecin derivatives are new compounds. Conclusion The modification of a 1,4-oxazine-2-one ring fused with positions 9 and 10 of Aring will reduce the antitumor activity of camptothecins.