| Antitumor agents. 280. Multidrug resistance-selective desmosdumotin B analogues. | |
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MedLine Citation:
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PMID: 20735140 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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6,6,8-Triethyldesmosdumotin B (2) was discovered as a MDR-selective flavonoid with significant in vitro anticancer activity against a multidrug resistant (MDR) cell line (KB-VIN) but without activity against the parent cells (KB). Additional 2 analogues were synthesized and evaluated to determine the effect of B-ring modifications on MDR-selectivity. Analogues with a B-ring Me (3) or Et (4) group had substantially increased MDR selectivity. Three new disubstituted analogues, 35, 37, and 49, also had high collateral sensitivity (CS) indices of 273, 250, and 100, respectively. Furthermore, 2-4 also displayed MDR selectivity in an MDR hepatoma-cell system. While 2-4 showed either no or very weak inhibition of cellular P-glycoprotein (P-gp) activity, they either activated or inhibited the actions of the first generation P-gp inhibitors verapamil or cyclosporin, respectively. |
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Authors:
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Kyoko Nakagawa-Goto; Po-Cheng Chang; Chin-Yu Lai; Hsin-Yi Hung; Tzu-Hsuan Chen; Pei-Chi Wu; Hao Zhu; Alexander Sedykh; Kenneth F Bastow; Kuo-Hsiung Lee |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 53 ISSN: 1520-4804 ISO Abbreviation: J. Med. Chem. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-16 Completed Date: 2010-10-11 Revised Date: 2012-04-26 |
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: 6699-705 Citation Subset: IM |
Affiliation:
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Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. goto@email.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 Apoptosis / drug effects Cell Line, Tumor Drug Resistance, Multiple* Drug Resistance, Neoplasm* Drug Screening Assays, Antitumor Flavones / chemical synthesis*, chemistry, pharmacology Humans P-Glycoprotein / biosynthesis Structure-Activity Relationship |
| Grant Support | |
ID/Acronym/Agency:
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CA-17625/CA/NCI NIH HHS; R01 CA017625-32/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/6,6,8-triethyldesmosdumotin B; 0/Antineoplastic Agents; 0/Flavones; 0/P-Glycoprotein |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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