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.
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.
Benyumov
Alexey O
AO
Departments of Embryology, Parker Hughes Institute, Roseville, MN 55113, USA.
Venkatachalam
Taracad K
TK
Grigoriants
Olga O
OO
Vassilev
Alexei O
AO
Tibbles
Heather E
HE
Downs
Suzanne
S
Dumezb
Darin
D
Uckun
Fatih M
FM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D061945:Caspase Inhibitors; D049109:Cell Proliferation / Q000187:drug effects; D054306:Dideoxynucleotides; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia / Q000188:drug therapy*; D009682:Magnetic Resonance Spectroscopy; D009391:Nephelometry and Turbidimetry; D011355:Prodrugs / Q000494:pharmacology; D013778:Tetrazolium Salts; D013844:Thiazoles; D013938:Thymidine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014404:Tubulin / Q000096:biosynthesis / Q000235:genetics; D015027:Zebrafish; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000494:pharmacology*
C114570:5-bromo-6-methoxy-5, 6-dihydro-3'-azidothymidine-5'-(p-bromophenyl) methoxyalaninyl phosphate; D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D054306:Dideoxynucleotides; D011355:Prodrugs; D013778:Tetrazolium Salts; D013844:Thiazoles; D014404:Tubulin; D013938:Thymidine Monophosphate; D015215:Zidovudine; C022616:thiazolyl blue