Design,synthesis, cytotoxic evaluation and tubulin inhibitory activity of 4-aryl-5-(3,4,5-trimethoxyphenyl)-2-alkylthio-1H-imidazole derivatives |
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| Authors: | Amir Assadieskandar Mohsen Amini Seyed Nasser Ostad Gholam Hossein Riazi Tayebe Cheraghi-Shavi Bentolhoda Shafiei Abbas Shafiee |
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| Affiliation: | 1. Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran;2. Department of Toxicology and Pharmacology, Faculty of Pharmacy and Rational Drug Use Research Center, Tehran University of Medical Sciences, Tehran, Iran;3. Neuroorganic Laboratory, Institute of Biochemistry and Biophysics, University of Tehran, Tehran 13145-1384, Iran;4. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran |
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| 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. |
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| Keywords: | Cytotoxicity activity Cell cycle analysis Tubulin polymerization Tautomerization |
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