| Convergent synthesis and biological evaluation of 2-amino-4-(3',4',5'-trimethoxyphenyl)-5-aryl thiazoles as microtubule targeting agents. | |
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MedLine Citation:
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PMID: 21663319 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Combretastatin A-4, a potent tubulin polymerization inhibitor, caused us to synthesize a novel series of 2-amino-4-(3',4',5'-trimethoxyphenyl)-5-aryl thiazoles with the goal of evaluating the effects of substituents on the phenyl at the 5-position of the thiazole skeleton on biological activities. An ethoxy group at the para-position produced the most active compound in the series, with IC(50) values of 0.03-0.9 nM against five of seven cancer cell lines. The most active compounds retained full activity in multidrug resistant cancer cells and acted through the colchicine site of tubulin. Treated cells were arrested in the G2/M phase of the cell cycle, with cell death proceeding through an apoptotic pathway that was only partially caspase-dependent. Preliminary results suggest that, in addition to cell death by apoptosis, cells were also killed via mitotic catastrophe as an alternative cell death mechanism. |
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Authors:
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Romeo Romagnoli; Pier Giovanni Baraldi; Andrea Brancale; Antonio Ricci; Ernest Hamel; Roberta Bortolozzi; Giuseppe Basso; Giampietro Viola |
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Publication Detail:
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Type: Journal Article Date: 2011-06-27 |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 54 ISSN: 1520-4804 ISO Abbreviation: J. Med. Chem. Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-07-21 Completed Date: 2011-10-10 Revised Date: 2013-04-12 |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: United States |
Other Details:
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Languages: eng Pagination: 5144-53 Citation Subset: IM |
Affiliation:
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Dipartimento di Scienze Farmaceutiche, Università di Ferrara, 44100 Ferrara, Italy. rmr@unife.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis Caspase Inhibitors Caspases / metabolism Cell Cycle / drug effects Cell Line, Tumor Cell Proliferation / drug effects Colchicine / chemistry Drug Resistance, Multiple Drug Resistance, Neoplasm Drug Screening Assays, Antitumor Enzyme Activation Humans Microtubules / drug effects* Mitosis Models, Molecular P-Glycoprotein / metabolism Protein Binding Structure-Activity Relationship Thiazoles / chemical synthesis*, chemistry, pharmacology Tubulin Modulators / chemical synthesis*, chemistry, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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Z99 CA999999/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Caspase Inhibitors; 0/P-Glycoprotein; 0/Thiazoles; 0/Tubulin Modulators; 64-86-8/Colchicine; EC 3.4.22.-/Caspases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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