Synthesis, characterization and antineoplastic activity of bis-aziridinyl dimeric naphthoquinone - A novel class of compounds with potent activity against acute myeloid leukemia cells.
Publication/Presentation Date
1-1-2017
Abstract
The synthesis, characterization and antileukemic activity of rationally designed amino dimeric naphthoquinone (BiQ) possessing aziridine as alkylating moiety is described. Bis-aziridinyl BiQ decreased proliferation of acute myeloid leukemia (AML) cell lines and primary cells from patients, and exhibited potent (nanomolar) inhibition of colony formation and overall cell survival in AML cells. Effective production of reactive oxygen species (ROS) and double stranded DNA breaks (DSB) induced by bis-aziridinyl BiQ is reported. Bis-dimethylamine BiQ, as the isostere of bis-aziridinyl BiQ but without the alkylating moiety did not show as potent anti-AML activity. Systemic administration of bis-aziridinyl BiQ was well tolerated in NSG mice.
Volume
27
Issue
1
First Page
6
Last Page
10
ISSN
1464-3405
Published In/Presented At
Carter-Cooper, B. A., Fletcher, S., Ferraris, D., Choi, E. Y., Kronfli, D., Dash, S., Truong, P., Sausville, E. A., Lapidus, R. G., & Emadi, A. (2017). Synthesis, characterization and antineoplastic activity of bis-aziridinyl dimeric naphthoquinone - A novel class of compounds with potent activity against acute myeloid leukemia cells. Bioorganic & medicinal chemistry letters, 27(1), 6–10. https://doi.org/10.1016/j.bmcl.2016.11.045
Disciplines
Medicine and Health Sciences
PubMedID
27890379
Department(s)
Department of Obstetrics and Gynecology, Department of Obstetrics and Gynecology Residents, Fellows and Residents
Document Type
Article