Antitumor agents 279. Structure-activity relationship and in vivo studies of novel 2-(furan-2-yl)naphthalen-1-ol (FNO) analogs as potent and selective anti-breast cancer agents.
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| Abstract |
In our ongoing modification study of neo-tanshinlactone (1), we discovered 2-(furan-2-yl)naphthalen-1-ol (FNO) derivatives 3 and 4 as a new class of anti-tumor agents. To explore structure-activity relationships (SAR) of this scaffold, 18 new analogs, 6-12 and 14-24, were designed and synthesized. The C11-esters 7 and 12 displayed broad anti-tumor activity (ED(50) 1.1-4.3 μg/mL against seven cancer cell lines), while C11-hydroxymethyl 14 showed unique selectivity against the SKBR-3 breast cancer cell line (ED(50) 0.73 μg/mL). Compounds 15 and 22 displayed potent and selective anti-breast tumor activity (ED(50) 1.7 and 0.85 μg/mL, respectively, against MDA-MB-231). The SAR results demonstrated that the substitutions from the ring-opened lactone ring C of 1 are critical to the anti-tumor potency as well as the apparent tumor-tissue type selectivity. Treatment with 3 in Brca1(f11/f11)p53(f5&6/f5&6)Cre(c) mice models significantly inhibited the proliferation of mammary epithelial cells and branching of mammary glands.
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| Authors | Yizhou Dong, Kyoko Nakagawa-Goto, Chin-Yu Lai, Yoon Kim, Susan L Morris-Natschke, Eva Y-H P Lee, Kenneth F Bastow, Kuo-Hsiung Lee |
| Journal | Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 21 Issue 1 Pg. 52-7 (Jan 01 2011) ISSN: 1464-3405 [Electronic] England |
| PMID | 21147529 (Publication Type: Journal Article, Research Support, N.I.H., Extramural) |
| Copyright | Copyright © 2010 Elsevier Ltd. All rights reserved. |
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