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

Alexey O. Benyumov, Taracad K. Venkatachalam, Olga O. Grigoriants, Alexei O. Vassilev, Heather E. Tibbles, Suzanne Downs, Darin Dumez, Fatih M. Uckun

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)114-122
Number of pages9
JournalArzneimittel-Forschung/Drug Research
Volume55
Issue number2
StatePublished - Mar 17 2005

Keywords

  • CAS 213982-96-8
  • DDE46, antileukemic activity, apoptosis, Zebrafish model
  • Zidovudine, bromomethoxylated arylphosphate derivative

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