Merck
  • Home
  • Search Results
  • [4-(imidazol-1-yl)thiazol-2-yl]phenylamines. A novel class of highly potent colchicine site binding tubulin inhibitors: synthesis and cytotoxic activity on selected human cancer cell lines.

[4-(imidazol-1-yl)thiazol-2-yl]phenylamines. A novel class of highly potent colchicine site binding tubulin inhibitors: synthesis and cytotoxic activity on selected human cancer cell lines.

Journal of medicinal chemistry (2006-09-15)
Siavosh Mahboobi, Andreas Sellmer, Heymo Höcher, Emerich Eichhorn, Thomas Bär, Mathias Schmidt, Thomas Maier, Josef F Stadlwieser, Thomas L Beckers
ABSTRACT

Synthesis and cytotoxic activity in the submicromolar range of a series of [4-(imidazol-1-yl)thiazol-2-yl]phenylamines are described. Cell cycle dependent cytotoxicity on RKO human colon carcinoma cells with inducible expression of p27(kip1) and the influence on microtubule formation were investigated. Considering the significant correlation between the IC(50) values of tubulin polymerization inhibition, [(3)H]colchicine competition, and cytotoxicity of the investigated compounds, tubulin is the main cellular target. The inhibition of microtubule formation was shown to be mediated by interference with the colchicine binding site of tubulin. In depth analysis of the investigated compounds allowed the identification of modifications that altered the pharmacological profile of the compounds from a mitosis-inducing phenotype to a G1 cell cycle arresting phenotype.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Podophyllotoxin
Sigma-Aldrich
Colchicine, ≥95% (HPLC), powder
Sigma-Aldrich
Colchicine, BioReagent, suitable for plant cell culture, ≥95% (HPLC)