Synthesis and antitumor activity of nitrogen-based thiocolchicine derivatives.
OBJECTIVE
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.


CONCLUSIONS
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.
Wang
Bin
B
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Pan
Xian-dao
XD
Liu
Hong-yan
HY
Yang
Jing
J
Lü
Zhao-yun
ZY
Zhao
Jing-hua
JH
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003078:Colchicine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008956:Models, Chemical; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D013329:Structure-Activity Relationship
D000972:Antineoplastic Agents, Phytogenic; C014856:thiocholchicine; D003078:Colchicine