The first series of 4,11-bis[(2-aminoethyl)amino]anthra[2,3-b]furan-5,10-diones: Synthesis and anti-proliferative characteristics

Abstract

We developed the synthesis of a series of furan-fused tetracyclic analogues of the antitumor agent ametantrone. The reactions included nucleophilic substitution of propoxy groups in 4,11-dipropoxyanthra[2,3-b]furan-5,10-diones with ethylenediamines, producing the derivatives of 4,11-diaminoanthra[2,3-b]furan-5,10-dione in good yields. Studies of anti-proliferative activity on a panel of mammalian tumor cell lines demonstrated that anthra[2,3-b]furan-5,10-diones were the most potent derivatives among heteroarene-fused ametantrone analogues with one heteroatom. We identified several compounds that evoked a growth inhibitory effect at submicromolar concentrations. The anthra[2,3-b]furan-5,10-dione 9 with distal methylamino groups was markedly potent against drug-resistant cell lines with P-glycoprotein overexpression or p53 gene deletion. Furthermore, this derivative attenuated in vitro topoisomerase I-mediated DNA uncoiling at low micromolar concentrations. These results demonstrate that anthrafurandiones are a new class of heterocyclic anthraquinone derivatives with the properties potentially valuable for anticancer therapy.

Acadesine Triggers Non-apoptotic Death in Tumor Cells

“…The MTT assay, staining with propidium iodide and Annexin V conjugated to fluorescein isothiocyanate (FITC ), determination of the cell cycle by flow cytofluorometry, and electrophoretic analysis of the integrity of genomic DNA were used to assess acadesine cytotoxicity [15, 16]. An apoptosis inductor, alkyl cationic glycerolipid rac- N- {4-[(2-ethoxy-3-octadecyloxy)prop-1-yloxycarbonyl] butyl}-N ’ -methylimidazolium iodide, was used as the control compound in individual experiments [17]. …”

Screening of Furanone in Cucurbita melo and Evaluation of its Bioactive Potential Using In Silico Studies

“…Chung et al [12] also reported benzonaphthofurandiones to be excellent inhibitors against topoisomerases II in cytotoxicity assay. According to Shchekotikhin et al [13], anthra[2.3-b]furan-5,10-dione with distal methylamino groups was potent against drug-resistant cell lines as it attenuated in vitro topoisomerase I-mediated DNA uncoiling at very low concentrations. Topoisomerase inhibition is a biological mechanism of action of most anthracyline drugs; topoisomerase I/II inhibition assay verified glycosylated 2-phenyl benzo[b]furans to be topoisomerase suppressors [14].…”

Pd-catalyzed cross-coupling/heterocyclization domino reaction: facile access to anthra[2,3-b]furan-5,10-dione scaffold

“…6,7 Previously, a series of linear furanoanthraquinones (anthra [2,3-b]furan-5,10-diones) was revealed as potent topoisomerase I poisons capable of inhibiting the growth of tumor cells with activated mechanisms of multidrug resistance. 8 It also has been found that a substituent at the 2-position of the heterocyclic core affects the cytotoxicity of these compounds. Several effective routes to the preparation anthra [2,3-b]furan-5,10-diones have been developed.…”