Novel valproic acid derivatives with potent differentiation-inducing activity in myeloid leukemia cells
2006; Elsevier BV; Volume: 30; Issue: 9 Linguagem: Inglês
10.1016/j.leukres.2006.01.009
ISSN1873-5835
AutoresHedwig E. Deubzer, Barbara Busche, Gabi Rönndahl, Daniel Eikel, Martin Michaelis, Jindřich Činátl, Sandra Schulze, Heinz Nau, Olaf Witt,
Tópico(s)HIV/AIDS drug development and treatment
ResumoThe anti-epileptic drug valproic acid harbors anti-tumoral activity in solid and leukemic tumor cell models and is currently evaluated in clinical trials. However, the plasma trough concentrations obtained in patients by common anti-epileptic dose regimens are below concentrations required for exerting anti-tumor effects in vitro. Here, we describe the identification of three novel valproic acid derivatives with superior differentiation-inducing and anti-proliferative activities in K562 bcr/abl-positive chronic myeloid leukemia cells and HL60 promyelocytic leukemia cells at achievable therapeutic VPA concentrations. These compounds reveal potent inhibition of histone deacetylase activity, induction of p21Cip/Waf expression as well as low toxicity on CD34+ bone marrow cells.
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