Design, synthesis, cytotoxic evaluation and tubulin inhibitory activity of 4-aryl-5-(3,4,5-trimethoxyphenyl)-2-alkylthio-1H-imidazole derivatives

作者：Assadieskandar Amir; Amini Mohsen; Ostad Seyed Nasser; Riazi Gholam Hossein; Cheraghi Shavi Tayebe; Shafiei Bentolhoda; Shafiee Abbas^*

来源：Bioorganic & Medicinal Chemistry, 2013, 21(10): 2703-2709.

DOI：10.1016/j.bmc.2013.03.011

• Cytotoxicity activity
• Cell cycle analysis
• Tubulin polymerization
• Tautomerization
• 2-Alkylthio-1H-imidazole

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 alpha,beta-tubulin through hydrogen bond interactions with Thr alpha 179 and Cys beta 241.

• 出版日期2013-5-15