Synthesis and cytotoxic properties of 4,11-bis[(aminoethyl)amino]anthra[2,3-b]thiophene-5,10-diones, novel analogues of antitumor anthracene-9,10-diones

Andrey E. Shchekotikhin, Valeria A. Glazunova, Lyubov G. Dezhenkova, Yuri N. Luzikov, Yuri B. Sinkevich, Leonid V. Kovalenko, Vladimir N. Buyanov, Jan Balzarini, Fong Chun Huang, Jing Jer Lin, Hsu Shan Huang, Alexander A. Shtil, Maria N. Preobrazhenskaya

Research output: Contribution to journalArticle

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Abstract

We developed the synthesis of a series of thiophene-fused tetracyclic analogues of the antitumor drug ametantrone. The reactions included nucleophilic substitution of methoxy groups in 4,11-dimethoxyanthra[2,3-b]thiophene-5,10-diones with ethylenediamines, producing the derivatives of 4,11-diaminoanthra[2,3-b]thiophene-5,10-dione in good yields. Several compounds showed marked antiproliferative potency against doxorubicin-selected, P-glycoprotein-expressing tumor cells and p53-/- cells. The cytotoxicity of some novel compounds for P-glycoprotein-positive cells is highly dependent on N-substituent at the terminal amino group of ethylenediamine moiety. The cytotoxic potency of selected compounds correlated with their ability to attenuate the functions of topoisomerase I and telomerase, strongly suggesting that these enzymes are the major targets of antitumor activity of anthra[2,3-b]thiophene-5,10-dione derivatives.

Original languageEnglish
Pages (from-to)1861-1869
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number5
DOIs
Publication statusPublished - Mar 1 2009
Externally publishedYes

Fingerprint

Thiophenes
ethylenediamine
P-Glycoprotein
ametantrone
Ethylenediamines
Cells
Derivatives
Type I DNA Topoisomerase
Telomerase
Cytotoxicity
Antineoplastic Agents
Doxorubicin
Tumors
Substitution reactions
heparinized hydrophilic polymer
anthracene
Enzymes
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Shchekotikhin, A. E., Glazunova, V. A., Dezhenkova, L. G., Luzikov, Y. N., Sinkevich, Y. B., Kovalenko, L. V., ... Preobrazhenskaya, M. N. (2009). Synthesis and cytotoxic properties of 4,11-bis[(aminoethyl)amino]anthra[2,3-b]thiophene-5,10-diones, novel analogues of antitumor anthracene-9,10-diones. Bioorganic and Medicinal Chemistry, 17(5), 1861-1869. https://doi.org/10.1016/j.bmc.2009.01.047

Synthesis and cytotoxic properties of 4,11-bis[(aminoethyl)amino]anthra[2,3-b]thiophene-5,10-diones, novel analogues of antitumor anthracene-9,10-diones. / Shchekotikhin, Andrey E.; Glazunova, Valeria A.; Dezhenkova, Lyubov G.; Luzikov, Yuri N.; Sinkevich, Yuri B.; Kovalenko, Leonid V.; Buyanov, Vladimir N.; Balzarini, Jan; Huang, Fong Chun; Lin, Jing Jer; Huang, Hsu Shan; Shtil, Alexander A.; Preobrazhenskaya, Maria N.

In: Bioorganic and Medicinal Chemistry, Vol. 17, No. 5, 01.03.2009, p. 1861-1869.

Research output: Contribution to journalArticle

Shchekotikhin, AE, Glazunova, VA, Dezhenkova, LG, Luzikov, YN, Sinkevich, YB, Kovalenko, LV, Buyanov, VN, Balzarini, J, Huang, FC, Lin, JJ, Huang, HS, Shtil, AA & Preobrazhenskaya, MN 2009, 'Synthesis and cytotoxic properties of 4,11-bis[(aminoethyl)amino]anthra[2,3-b]thiophene-5,10-diones, novel analogues of antitumor anthracene-9,10-diones', Bioorganic and Medicinal Chemistry, vol. 17, no. 5, pp. 1861-1869. https://doi.org/10.1016/j.bmc.2009.01.047
Shchekotikhin, Andrey E. ; Glazunova, Valeria A. ; Dezhenkova, Lyubov G. ; Luzikov, Yuri N. ; Sinkevich, Yuri B. ; Kovalenko, Leonid V. ; Buyanov, Vladimir N. ; Balzarini, Jan ; Huang, Fong Chun ; Lin, Jing Jer ; Huang, Hsu Shan ; Shtil, Alexander A. ; Preobrazhenskaya, Maria N. / Synthesis and cytotoxic properties of 4,11-bis[(aminoethyl)amino]anthra[2,3-b]thiophene-5,10-diones, novel analogues of antitumor anthracene-9,10-diones. In: Bioorganic and Medicinal Chemistry. 2009 ; Vol. 17, No. 5. pp. 1861-1869.
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