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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2011-3-3
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pubmed:abstractText |
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 ?M. 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 ?M, 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 ?M and colchicine binding by 78% as well as cellular microtubule polymerization and spindle formation.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1520-4804
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pubmed:author |
pubmed-author:BastowKenneth FKF,
pubmed-author:GotoMasuoM,
pubmed-author:HamelErnestE,
pubmed-author:KozakaTakashiT,
pubmed-author:LaiChin-YuCY,
pubmed-author:LeeKuo-HsiungKH,
pubmed-author:Nakagawa-GotoKyokoK,
pubmed-author:OhkoshiEmikaE,
pubmed-author:WuPei-ChiPC,
pubmed-author:ZhangLiyingL,
pubmed-author:ZhuHaoH
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pubmed:issnType |
Electronic
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pubmed:day |
10
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pubmed:volume |
54
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1244-55
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pubmed:meshHeading |
pubmed-meshheading:21284385-Antineoplastic Agents,
pubmed-meshheading:21284385-Cell Line, Tumor,
pubmed-meshheading:21284385-Chromones,
pubmed-meshheading:21284385-Colchicine,
pubmed-meshheading:21284385-Drug Resistance, Multiple,
pubmed-meshheading:21284385-Drug Resistance, Neoplasm,
pubmed-meshheading:21284385-Drug Screening Assays, Antitumor,
pubmed-meshheading:21284385-Humans,
pubmed-meshheading:21284385-Naphthalenes,
pubmed-meshheading:21284385-Protein Binding,
pubmed-meshheading:21284385-Structure-Activity Relationship,
pubmed-meshheading:21284385-Thiophenes,
pubmed-meshheading:21284385-Tubulin,
pubmed-meshheading:21284385-Tubulin Modulators
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pubmed:year |
2011
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pubmed:articleTitle |
Antitumor agents. 284. New desmosdumotin B analogues with bicyclic B-ring as cytotoxic and antitubulin agents.
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pubmed:affiliation |
Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States. Ken_Bastow@unc.edu
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pubmed:publicationType |
Journal Article
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