1.
Bioorg Med Chem
; 21(10): 2703-9, 2013 May 15.
Artigo
em Inglês
| MEDLINE
| ID: mdl-23566762
RESUMO
A new series of 4-aryl-5-(3,4,5-trimethoxyphenyl)-2-alkylthio-1H-imidazoles were synthesized and their cytotoxic activities in vitro against four different cell lines (HT-29, MCF-7, NIH-3T3, AGS) were evaluated. Compound 6g bearing 3,4,5-trimethoxyphenyl moiety on ring A and 4-methoxy substituent on ring B displayed potent cytotoxic activity against all cell lines. Flow cytometry analysis and microtubule polymerization assay confirmed that cytotoxic activities of this compound were related to inhibitory effect against microtubules polymerization. Molecular modeling studies revealed that compound 6g could strongly bind to the colchicine binding site of α,ß-tubulin through hydrogen bond interactions with Thrα179 and Cysß241.