کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1360666 | 981443 | 2009 | 9 صفحه PDF | دانلود رایگان |
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.
The preparation and cytotoxic properties of novel series of 4,11-bis[(aminoethyl)amino]anthra[2,3-b]thiophene-5,10-diones are described. The anthra[2,3-b]thiophene-5,10-diones carrying N-methyl- or N,N-dimethylamino groups at the side chains demonstrated a remarkable activity against drug resistant tumor cells. The derivatives with guanidine groups in the side chains were identified as potent inhibitors of telomerase activity.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 17, Issue 5, 1 March 2009, Pages 1861–1869