Synthesis, characterization and antineoplastic activity of bis-aziridinyl dimeric naphthoquinone - A novel class of compounds with potent activity against acute myeloid leukemia cells

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• 作者：Brandon A. Carter-Cooper^a ; Steven Fletcher^b ; Dana Ferraris^c ; Eun Yong Choi^a ; Dahlia Kronfli^a ; Smaraki Dash^a ; Phuc Truong^c ; Edward A. Sausville^a ; Rena G. Lapidus^a ; Ashkan Emadi^a ; ^{aemadi@umm.edu}
• 关键词：Naphthoquinone ; Acute myeloid leukemia ; DNA damage ; Reactive oxygen species ; Aziridine
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2017
• 出版时间：1 January 2017
• 年：2017
• 卷：27
• 期：1
• 页码：6-10
• 全文大小：746 K
• 卷排序：27

文摘

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.