Document Detail

Antitumor agents. 284. New desmosdumotin B analogues with bicyclic B-ring as cytotoxic and antitubulin agents.
MedLine Citation:
PMID:  21284385     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article     Date:  2011-02-01
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  54     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-03     Completed Date:  2011-06-06     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1244-55     Citation Subset:  IM    
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MeSH Terms
Antineoplastic Agents / 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
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
R01 CA017625/CA/NCI NIH HHS; R01 CA017625-32/CA/NCI NIH HHS
Reg. No./Substance:
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; SML2Y3J35T/Colchicine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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