MedChemComm p. 452 - 458 (2014)
Update date:2022-07-29
Topics:
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
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.
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