4-Chlorocolchicine derivatives bearing a thiourea side chain at the C-7 position as potent anticancer agentsElectronic supplementary information (ESI) available: Synthetic procedures and characterization data of all compounds, as well as the methodology used in cytotoxicity evaluation, antitumor experiments, metabolic stability experiments, and docking simulations. See DOI: 10.1039/c3md00287j

• Main Authors: Nishiyama, Hiroyuki, Ono, Masahiro, Sugimoto, Takuya, Sasai, Toshio, Asakawa, Naoyuki, Ueno, Satoshi, Tominaga, Yoshitaka, Yaegashi, Takashi, Nagaoka, Masato, Matsuzaki, Takeshi, Kogure, Noriyuki, Kitajima, Mariko, Takayama, Hiromitsu
• Format: Article
• Language: English
• ISSN: 2040-2503; 2040-2511
• DOI: 10.1039/c3md00287j

A series of 4-substituted colchicine derivatives were synthesized and evaluated with an eye toward developing new anticancer agents. As a result, 4-chlorocolchicine derivatives bearing a thioureide side chain at the C-7 position were found to exhibit significant cytotoxicities to three human cancer cell lines (A549, HT-29, and HCT116). In particular, compound 26 having an ethylthioureide group at the C-7 had high antitumor activity in vivo and a broad effective dosage range. Furthermore, compound 58 , which has a (5-methylpyrazol-3-yl)thioureide group at the C-7 side chain, exhibited strong cytotoxicity and desirable metabolic stability in vitro . 4-Chlorocolchicines bearing a thioureide group at the C-7 side chain showed high potencies in vitro and in vivo .