The first series of 4,11-bis[(2-aminoethyl)amino]anthra[2,3-b]furan-5,10- diones

Synthesis and anti-proliferative characteristics

Andrey E. Shchekotikhin, Valeria A. Glazunova, Lyubov G. Dezhenkova, Elena K. Shevtsova, Valery F. Traven', Jan Balzarini, Hsu Shan Huang, Alexander A. Shtil, Maria N. Preobrazhenskaya

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)423-428
Number of pages6
JournalEuropean Journal of Medicinal Chemistry
Volume46
Issue number1
DOIs
Publication statusPublished - Jan 2011
Externally publishedYes

Fingerprint

ametantrone
Derivatives
Ethylenediamines
Cells
Anthraquinones
Type I DNA Topoisomerase
p53 Genes
Gene Deletion
P-Glycoprotein
Tumor Cell Line
Antineoplastic Agents
Tumors
Substitution reactions
Genes
heparinized hydrophilic polymer
furan
Cell Line
DNA
Growth
Pharmaceutical Preparations

Keywords

  • Anthra[2,3-b]furan-5,10-diones
  • Cytotoxicity
  • Drug resistance
  • Topoisomerase I
  • Tumor cells

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Shchekotikhin, A. E., Glazunova, V. A., Dezhenkova, L. G., Shevtsova, E. K., Traven', V. F., Balzarini, J., ... Preobrazhenskaya, M. N. (2011). The first series of 4,11-bis[(2-aminoethyl)amino]anthra[2,3-b]furan-5,10- diones: Synthesis and anti-proliferative characteristics. European Journal of Medicinal Chemistry, 46(1), 423-428. https://doi.org/10.1016/j.ejmech.2010.11.017

The first series of 4,11-bis[(2-aminoethyl)amino]anthra[2,3-b]furan-5,10- diones : Synthesis and anti-proliferative characteristics. / Shchekotikhin, Andrey E.; Glazunova, Valeria A.; Dezhenkova, Lyubov G.; Shevtsova, Elena K.; Traven', Valery F.; Balzarini, Jan; Huang, Hsu Shan; Shtil, Alexander A.; Preobrazhenskaya, Maria N.

In: European Journal of Medicinal Chemistry, Vol. 46, No. 1, 01.2011, p. 423-428.

Research output: Contribution to journalArticle

Shchekotikhin, AE, Glazunova, VA, Dezhenkova, LG, Shevtsova, EK, Traven', VF, Balzarini, J, Huang, HS, Shtil, AA & Preobrazhenskaya, MN 2011, 'The first series of 4,11-bis[(2-aminoethyl)amino]anthra[2,3-b]furan-5,10- diones: Synthesis and anti-proliferative characteristics', European Journal of Medicinal Chemistry, vol. 46, no. 1, pp. 423-428. https://doi.org/10.1016/j.ejmech.2010.11.017
Shchekotikhin, Andrey E. ; Glazunova, Valeria A. ; Dezhenkova, Lyubov G. ; Shevtsova, Elena K. ; Traven', Valery F. ; Balzarini, Jan ; Huang, Hsu Shan ; Shtil, Alexander A. ; Preobrazhenskaya, Maria N. / The first series of 4,11-bis[(2-aminoethyl)amino]anthra[2,3-b]furan-5,10- diones : Synthesis and anti-proliferative characteristics. In: European Journal of Medicinal Chemistry. 2011 ; Vol. 46, No. 1. pp. 423-428.
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