Document Detail

In vitro cytotoxic activity of novel protoflavone analogs - selectivity towards a multidrug resistant cancer cell line.
MedLine Citation:
PMID:  22753749     Owner:  NLM     Status:  In-Data-Review    
BACKGROUND: Protoapigenone (PA), a natural flavonoid possessing an unusual p-quinol moiety on its B ring, is a prospective novel lead compound against cancer currently in development, together with WYC0209, a potent synthetic PA analog. Structure activity relationships (SAR) concerning different 1'-O-alkyl side-chains were also studied on two sets of derivatives.
MATERIALS AND METHODS: Fifteen 1'-O-alkyl protoflavone derivatives were synthesized from genkwanin or 4'-hydroxy-6-methylflavone, thirteen of which are new compounds. All compounds were tested for their cytotoxic effect on four human cancer cell lines, such as HepG2 and Hep3B (hepatic), A549 (lung) and MDA-MB-231 (breast) cell lines, with doxorubicin as a positive control. All compounds, as well as PA, WYC0209 and fourteen of their previously reported analogs were also tested on a multidrug-resistant (MDR) sub-cell line of L5178 mouse T-cell lymphoma and on its parental counterpart (PAR).
RESULTS: In general, derivatives bearing a free hydroxyl group at C-1' exerted the strongest activities, while C-1'-substituted compounds were found to be much weaker. Derivatives of 6-methylflavone exhibited mild, but statistically significant selectivity towards the MDR cell line.
CONCLUSION: The results are in agreement with our previous findings for fundamental SAR of protoflavones. 6-Methylated protoflavones may serve as valuable leads for developing selective compounds against MDR cancer. Identical activity of other derivatives on the PAR and MDR cell lines suggests that cancer cells cannot exhibit resistance to protoflavones by ABCB1 efflux pump overexpression.
B Danko; A Martins; D W Chuang; H C Wang; L Amaral; J Molnár; F R Chang; Y C Wu; A Hunyadi
Related Documents :
10364209 - Phosphorylation of the myosin-ii light chain does not regulate the timing of cytokinesi...
2612379 - Control of cell type proportions by a secreted factor in dictyostelium discoideum.
1706999 - De novo formation of cytokeratin filaments in calf lens cells and cytoplasts after tran...
17637359 - Bacterial swarming: a re-examination of cell-movement patterns.
1850369 - A possible role for dif-2 in the formation of stalk cells during dictyostelium developm...
2797149 - Myosin i is located at the leading edges of locomoting dictyostelium amoebae.
155659 - Inhibition of mixed-lymphocyte reaction by quinine and lack of effect on plaque-forming...
11118429 - The cellular uptake of anandamide is coupled to its breakdown by fatty-acid amide hydro...
457749 - Studies on the function of cell surface glycoproteins. ii. possible role of surface gly...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anticancer research     Volume:  32     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-03     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  2863-9     Citation Subset:  IM    
Faculty of Pharmacy, University of Szeged, 6720 Szeged, Eötvös Str. 6, Hungary. Tel: +36 62546456,
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

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

Previous Document:  Anti-invasive Effects and Proapoptotic Activity Induction by the Rexinoid IIF and Valproic Acid in C...
Next Document:  The organic arsenic derivative GMZ27 induces PML-RAR?-independent apoptosis in myeloid leukemia cell...