PUBLICATION

Anti-proliferative and anti-leukemic activity of DDE46 (compound WHI-07), a novel bromomethoxylated arylphosphate derivative of zidovudine, and related compounds. Studies using human acute lymphoblastic leukemia cells and the zebrafish model

Authors
Benyumov, A.O., Venkatachalam, T.K., Grigoriants, O.O., Vassilev, A.O., Tibbles, H.E., Downs, S., Dumezb, D., and Uckun, F.M.
ID
ZDB-PUB-050328-7
Date
2005
Source
Arzneimittel-Forschung   55(2): 114-122 (Journal)
Registered Authors
Benyumov, Alexey O.
Keywords
none
MeSH Terms
  • Animals
  • Antineoplastic Agents/pharmacology*
  • Antineoplastic Agents/therapeutic use
  • Apoptosis/drug effects
  • Caspase Inhibitors
  • Cell Proliferation/drug effects
  • Dideoxynucleotides
  • Drug Screening Assays, Antitumor
  • Humans
  • Jurkat Cells
  • Leukemia/drug therapy*
  • Magnetic Resonance Spectroscopy
  • Nephelometry and Turbidimetry
  • Prodrugs/pharmacology
  • Tetrazolium Salts
  • Thiazoles
  • Thymidine Monophosphate/analogs & derivatives*
  • Thymidine Monophosphate/pharmacology*
  • Tubulin/biosynthesis
  • Tubulin/genetics
  • Zebrafish
  • Zidovudine/analogs & derivatives*
  • Zidovudine/pharmacology*
PubMed
15787279 Full text @ Arzneimittelforschung
Abstract
The anti-proliferative effects of a novel bromomethoxylated arylphosphate derivative of zidovudine (compound DDE46, CAS 213982-96-8) were first examined in a zebra fish embryo model. DDE46 blocked the cell division at the 2-cell stage of the embryonic development followed by total cell fusion. DDE46 also inhibited the proliferation of the leukemic cell lines NALM-6 and MOLT-3. DDE46 enhanced the activity of the pro-apoptotic enzymes Caspase-3, Caspase-6, Caspase-8, and Caspase-9 leading to the apoptotic death of the leukemic cell line Jurkat. These results justify the further development of this agent as a new anti-leukemic drug candidate.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping