4855-05-4Relevant articles and documents
Benzoylurea derivatives as a novel class of antimitotic agents: Synthesis, anticancer activity, and structure-activity relationships
Song, Dan-Qing,Wang, Yan,Wu, Lian-Zong,Yang, Peng,Wang, Yue-Ming,Gao, Li-Mei,Li, Yan,Qu, Jing-Rong,Wang, Yong-Hong,Li, Ying-Hong,Du, Na-Na,Han, Yan-Xing,Zhang, Zhi-Ping,Jiang, Jian-Dong
scheme or table, p. 3094 - 3103 (2009/04/06)
Forty-six new compounds were synthesized on the basis of our knowledge of the 3-haloacylamino benzoylurea (HBU) series. Structure-activity relationship (SAR) analysis indicates that (i) the configuration of the chiral center in 1 (JIMB01) is not indispensable for the activity, (ii) the phenyl ring is essential, and (iii) a substitution at the 6-position of the phenyl ring with a halogen enhances the activity. Among the analogues, 11e and 14b bearing 6-fluoro substitution showed potent activities against nine human tumor cell lines, including CEM (leukemia), Daudi (lymphoma), MCF-7 (breast cancer), Bel-7402 (hepatoma), DU-145 (prostate cancer), PC-3 (prostate cancer), DND-1A(melanoma), LOVO (colon cancer), and MIA Paca (pancreatic cancer) with IC50 values between 0.01 and 0.30 μM. 14b inhibited human hepatocarcinoma by 86% in volume in nude mice. The mechanism of 14b is to inhibit microtubule assembly, followed by the M-phase arrest, bcl-2 inactivation, and then apoptosis. We consider 14b promising for further anticancer investigation.
