Document Detail

Antitumor agents. 280. Multidrug resistance-selective desmosdumotin B analogues.
MedLine Citation:
PMID:  20735140     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  53     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-16     Completed Date:  2010-10-11     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:  6699-705     Citation Subset:  IM    
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MeSH Terms
Antineoplastic Agents / 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
P-Glycoprotein / biosynthesis
Structure-Activity Relationship
Grant Support
CA-17625/CA/NCI NIH HHS; R01 CA017625/CA/NCI NIH HHS; R01 CA017625-32/CA/NCI NIH HHS
Reg. No./Substance:
0/6,6,8-triethyldesmosdumotin B; 0/Antineoplastic Agents; 0/Flavones; 0/P-Glycoprotein

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

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