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
Citation
Benyumov, A.O., Venkatachalam, T.K., Grigoriants, O.O., Vassilev, A.O., Tibbles, H.E., Downs, S., Dumezb, D., and Uckun, F.M. (2005) 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. Arzneimittel-Forschung. 55(2):114-122.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping