| Antitumor agents. 284. New desmosdumotin B analogues with bicyclic B-ring as cytotoxic and antitubulin agents. | |
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MedLine Citation:
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PMID: 21284385 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We previously reported that the biological activity of analogues of desmosdumotin B (1) was dramatically changed depending on the B-ring system. A naphthalene B-ring analogue 3 exerted potent in vitro activity against a diverse panel of human tumor cell lines with GI(50) values of 0.8-2.1 μM. In contrast, 1 analogues with a phenyl B-ring showed unique selective activity against P-glycoprotein (P-gp) overexpressing multidrug resistant cell line. We have now prepared and evaluated 1 analogues with bicyclic or tricyclic aromatic B-ring systems as in vitro inhibitors of human cancer cell line proliferation. Among all synthesized derivatives, 21 with a benzo[b]thiophenyl B-ring was highly active, with GI(50) values of 0.06-0.16 μM, and this activity was not influenced by overexpression of P-gp. Furthermore, 21 inhibited tubulin assembly in vitro with an IC(50) value of 2.0 μM and colchicine binding by 78% as well as cellular microtubule polymerization and spindle formation. |
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Authors:
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Kyoko Nakagawa-Goto; Pei-Chi Wu; Chin-Yu Lai; Ernest Hamel; Hao Zhu; Liying Zhang; Takashi Kozaka; Emika Ohkoshi; Masuo Goto; Kenneth F Bastow; Kuo-Hsiung Lee |
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Publication Detail:
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Type: Journal Article Date: 2011-02-01 |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 54 ISSN: 1520-4804 ISO Abbreviation: J. Med. Chem. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-03-03 Completed Date: 2011-06-06 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: 1244-55 Citation Subset: IM |
Affiliation:
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Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States. Ken_Bastow@unc.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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chemical synthesis*,
chemistry,
pharmacology Cell Line, Tumor Chromones / chemical synthesis*, chemistry, pharmacology Colchicine / chemistry Drug Resistance, Multiple / drug effects Drug Resistance, Neoplasm / drug effects Drug Screening Assays, Antitumor Humans Naphthalenes / chemical synthesis, chemistry, pharmacology Protein Binding Structure-Activity Relationship Thiophenes / chemical synthesis*, chemistry, pharmacology Tubulin / chemistry Tubulin Modulators / chemical synthesis, chemistry, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA017625-32/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/2-(benzo(b)thiophen-3'-yl)-6,8,8-triethyldesmosdumotin B; 0/Antineoplastic Agents; 0/Chromones; 0/Naphthalenes; 0/Thiophenes; 0/Tubulin; 0/Tubulin Modulators; 64-86-8/Colchicine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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