Document Detail

Development of nonsymmetrical 1,4-disubstituted anthraquinones that are potently active against cisplatin-resistant ovarian cancer cells.
MedLine Citation:
PMID:  16220985     Owner:  NLM     Status:  MEDLINE    
A novel series of 1,4-disubstituted aminoanthraquinones were prepared by ipso-displacement of 1,4-difluoro-5,8-dihydroxyanthraquinones by hydroxylated piperidinyl- or pyrrolidinylalkylamino side chains. One aminoanthraquinone (13) was further derivatized to a chloropropylamino analogue by treatment with triphenylphosphine-carbon tetrachloride. The compounds were evaluated in the A2780 ovarian cancer cell line and its cisplatin-resistant variants (A2780/cp70 and A2780/MCP1). The novel anthraquinones were shown to possess up to 5-fold increased potency against the cisplatin-resistant cells compared to the wild-type cells. Growth curve analysis of the hydroxyethylaminoanthraquinone 8 in the osteosarcoma cell line U-2 OS showed that the cell cycle is not frozen, rather there is a late cell cycle arrest consistent with the action of a DNA-damaging topoisomerase II inhibitor. Accumulative apoptotic events, using time lapse photography, indicate that 8 is capable of fully engaging cell cycle arrest pathways in G2 in the absence of early apoptotic commitment. 8 and its chloropropyl analogue 13 retained significant activity against human A2780/cp70 xenografted tumors in mice.
Klaus Pors; Jane A Plumb; Robert Brown; Paul Teesdale-Spittle; Mark Searcey; Paul J Smith; Laurence H Patterson
Related Documents :
6242755 - Genetics of the mammalian oxidative phosphorylation system: characterization of a new o...
20031255 - Cadmium has contrasting effects on polyethylene glycol-sensitive and resistant cell lin...
17639045 - Induction of multidrug resistance associated protein 2 in tamoxifen-resistant breast ca...
21521445 - Corneal invasion by hemangiosarcoma in a horse.
18222625 - Bovine herpesvirus type 1 induces cell death by a cell-type-dependent fashion.
20102605 - Differences in the transcriptome signatures of two genetically related entamoeba histol...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  48     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-10-13     Completed Date:  2005-12-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6690-5     Citation Subset:  IM    
Department of Pharmaceutical and Biological Chemistry, The School of Pharmacy, University of London, 29-39 Brunswick Square, London.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Anthraquinones / chemical synthesis*,  chemistry,  pharmacology
Antigens, Neoplasm
Antineoplastic Agents / chemical synthesis*,  chemistry,  pharmacology
Cisplatin / pharmacology*
DNA Topoisomerases, Type II, Eukaryotic / antagonists & inhibitors
DNA-Binding Proteins / antagonists & inhibitors
Drug Resistance, Neoplasm
Drug Screening Assays, Antitumor
Mice, Nude
Ovarian Neoplasms
Structure-Activity Relationship
Transplantation, Heterologous
Reg. No./Substance:
0/1-((2-dimethylamino)ethylamino)-4-(2-(3-hydroxymethylpiperidin-1-yl)ethylamino)-5,8-dihydroxyanthracene-9,10-dione; 0/Anthraquinones; 0/Antigens, Neoplasm; 0/Antineoplastic Agents; 0/DNA-Binding Proteins; 15663-27-1/Cisplatin; EC 5.99.1.-/DNA Topoisomerases, Type II, Eukaryotic; EC topoisomerase II alpha

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

Previous Document:  Antibiotic binding to monozinc CphA beta-lactamase from Aeromonas hydropila: quantum mechanical/mole...
Next Document:  Perhydroquinolylbenzamides as novel inhibitors of 11beta-hydroxysteroid dehydrogenase type 1.