title: Design, synthesis, cytotoxic evaluation and tubulin inhibitory activity of 4-aryl-5-(3,4,5-trimethoxyphenyl)-2-alkylthio-1H-imidazole derivatives.
abstract: 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,β-tubulin through hydrogen bond interactions with Thrα179 and Cysβ241.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Assadieskandar
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.forename: Seyed Nasser
authors.initials: SN
authors.lastname: Ostad
authors.forename: Gholam Hossein
authors.initials: GH
authors.lastname: Riazi
authors.forename: Tayebe
authors.initials: T
authors.lastname: Cheraghi-Shavi
authors.forename: Bentolhoda
authors.initials: B
authors.lastname: Shafiei
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
mesh_terms: D015195:Drug Design; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008870:Microtubules; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D007093:Imidazoles; D050257:Tubulin Modulators; C029899:imidazole