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

研究成果: 雜誌貢獻文章同行評審

37 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)1861-1869
頁數9
期刊Bioorganic and Medicinal Chemistry
17
發行號5
DOIs
出版狀態已發佈 - 三月 1 2009
對外發佈

ASJC Scopus subject areas

  • 藥學科學
  • 藥物發現
  • 有機化學
  • 分子醫學
  • 分子生物學
  • 臨床生物化學
  • 生物化學

指紋

深入研究「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」主題。共同形成了獨特的指紋。

引用此