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

作者：Dong Yizhou; Nakagawa Goto Kyoko; Lai Chin Yu; Kim Yoon; Morris Natschke Susan L; Lee Eva Y H P^*; Bastow Kenneth F; Lee Kuo Hsiung

来源：Bioorganic & Medicinal Chemistry Letters, 2011, 21(1): 52-57.

DOI：10.1016/j.bmcl.2010.11.077

• 2-(Furan-2-yl)naphthalen-1-ol analogs
• Structure-activity relationships
• Anti-breast tumor agents

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 mu g/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 mu g/mL). Compounds 15 and 22 displayed potent and selective anti-breast tumor activity (ED(50) 1.7 and 0.85 mu g/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/

• 出版日期2011-1
• 单位中国医科大学