کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1360464 | 981437 | 2009 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Synthesis and activity evaluation of phenylurea derivatives as potent antitumor agents Synthesis and activity evaluation of phenylurea derivatives as potent antitumor agents](/preview/png/1360464.png)
We have discovered several tubulin-active compounds in our previous studies. In the establishment of a compound library of small molecule weight tubulin ligands, 14 new N-3-haloacylaminophenyl-N′-(alkyl/aryl) urea analogs were designed and synthesized. The structure–activity relationship (SAR) analysis revealed that (i) the order of anticancer potency for the 3-haloacylamino chain was following –CH2Br > –CHBrCH3; (ii) the N′-substituent moiety was not essential for the anticancer activity, and a proper alkyl substitution might enhance the anticancer activity. Among these analogs, the compounds 16j bearing bromoacetyl at the N′-end exhibited a potent activity against eight human tumor cell lines, including CEM (leukemia), Daudi (lymphoma), MCF-7 (breast cancer), Bel-7402 (hepatoma), DU-145 (prostate cancer), DND-1A (melanoma), LOVO (colon cancer) and MIA Paca (pancreatic cancer), with the IC50 values between 0.38 and 4.07 μM. Interestingly, compound 16j killed cancer cells with a mechanism independent of the tubulin-based mechanism, indicating a significant change of the action mode after the structure modification.
The phenylurea derivatives were designed, synthesized and evaluated for the anticancer activities as a class of β-tubulin ligands. However, they change the mode of action from tubulin-based mechanism to the one different from their parent compounds.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 17, Issue 11, 1 June 2009, Pages 3873–3878