Synthesis and in vitro antitumor activities of novel benzyl urea analogues of sorafenib.
- Author:
Chen-Shu LU
1
;
Ke TANG
;
Yan LI
;
Bo JIN
;
Da-Li YIN
;
Chen MA
;
Xiao-Guang CHEN
;
Hai-Hong HUANG
Author Information
1. Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
Antineoplastic Agents;
chemical synthesis;
chemistry;
pharmacology;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
Drug Screening Assays, Antitumor;
HT29 Cells;
Humans;
Inhibitory Concentration 50;
Molecular Structure;
Niacinamide;
analogs & derivatives;
chemical synthesis;
chemistry;
pharmacology;
Phenylurea Compounds;
chemical synthesis;
chemistry;
pharmacology;
Solubility;
Structure-Activity Relationship;
Urea;
analogs & derivatives;
chemical synthesis;
chemistry;
pharmacology
- From:
Acta Pharmaceutica Sinica
2013;48(5):709-717
- CountryChina
- Language:English
-
Abstract:
A novel series of benzyl urea analogues based on the structural modification of sorafenib were synthesized. Their in vitro antitumor activities against MX-1, HepG2, Ketr3 and HT-29 were evaluated using the standard MTT assay. While several target compounds showed inhibitory activity against multiple cancer cell lines, compound 9 was of particular interest, demonstrating IC50 values (5.69-13.6 micromol x L(-1)) comparable to those of sorafenib. Furthermore, compounds 20 and 23 showed more potent inhibitory activity against HT-29 and MX-1 when compared to sorafenib. In particular, compound 20 bearing the N-3-pyridyl moiety not only exhibited greater inhibitory activity against HT-29 cell line (IC50 3.82 micromol x L(-1)), but also had improved solubility at pH 7.2, is worthy of further investigation as a lead to identify novel antitumor agents.
