Synthesis and activity evaluation of benzoylurea derivatives as potential antiproliferative agents.
Bioorg Med Chem Lett
; 19(3): 755-8, 2009 Feb 01.
Article
en En
| MEDLINE
| ID: mdl-19111465
ABSTRACT
3-Haloacylamino benzoylureas (3-HBUs) consist of a new family of tubulin ligands that kill cancer cells through mitotic arrest. In exploring the structure-activity relationship (SAR), 17 analogues defined through variations of formylurea at the 1-position of the aromatic ring were synthesized. SAR analysis revealed that (i) the p-pi conjugation between the aromatic ring and formylurea was essential; (ii) suitable aryl substitutions at the N'-end increased anticancer activity with a mechanism different from that of parent compounds; and (iii) introduction of pyridyl at the N'-end provided an opportunity of making soluble salts to improve bioavailability. Among the analogues, 16c bearing 3,4,5-trimethoxyphenyl and 16g bearing 2-pyridyl at the N'-end showed an enhanced activity and were active in hepatoma cells that were resistant to tubulin ligands including the parent compounds. Furthermore, 16c and 16g killed cancer cells with a mechanism independent of mitotic arrest, indicating a change of action mode.
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Bases de datos:
MEDLINE
Asunto principal:
Urea
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Química Farmacéutica
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Neoplasias
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Antineoplásicos
Idioma:
En
Revista:
Bioorg Med Chem Lett
Año:
2009
Tipo del documento:
Article
País de afiliación:
China