Synthesis and Characterization of 4,11-Diaminoanthra[2,3‑b]furan- 5,10-diones: Tumor Cell Apoptosis through tNOX-Modulated NAD+/ NADH Ratio and SIRT1статья
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 7 ноября 2016 г.
Аннотация:A series of new 4,11-diaminoanthra[2,3-b]furan-5,10-dione derivatives with different side chains were synthesized.Selected 2-unsubstituted derivatives 11−14 showed high antiproliferative potency on a panel of mammalian tumor cell lines including multidrug resistance variants. Compounds 11−14 utilized multiple mechanisms of cytotoxicity including inhibition of Top1/Top2-mediated DNA relaxation, reduced NAD+/NADH ratio through tNOX inhibition, suppression of a NAD+- dependent sirtuin 1 (SIRT1) deacetylase activity, and activation of caspase-mediated apoptosis. Here, for the first time, we report that tumor-associated NADH oxidase (tNOX) and SIRT1 are important cellular targets of antitumor anthracene-9,10-diones.