Antitumor Agents. 254. Synthesis and Biological Evaluation of Novel Neo-tanshinlactone Analogues as Potent Anti-Breast Cancer Agents
详细信息 查看全文
- 作者：Xihong Wang ; Kyoko Nakagawa-Goto ; Kenneth F. Bastow ; Ming-Jaw Don ; Yun-Lian Lin ; Tian-Shung Wu ; Kuo-Hsiung Lee
- 刊名：Journal of Medicinal Chemistry
- 出版年：2006
- 出版时间：September 7, 2006
- 年：2006
- 卷：49
- 期：18
- 页码：5631 - 5634
- 全文大小：66K
- 年卷期：v.49,no.18(September 7, 2006)
- ISSN：1520-4804
文摘
In our previous study, neo-tanshinlactone (1) showed potent and selective anti-breast cancer activity. Toexplore the SAR of 1, nine analogues (15-18, 24-28) were designed and synthesized. Together with 1 andtamoxifen (TAM), all newly synthesized compounds and some intermediates were evaluated for in vitroanticancer activity against several human tumor cell lines. Compounds without a ring D did not showpromising activity, while compounds with a methylated furan ring D showed better activity than those withunsubstituted furan or hydroxy-dihydrofuran rings. Among all newly synthesized compounds, compound15 with an ethyl group at the 4-position showed the best activity and selectivity with ED50 values of 0.45and 0.18 
g/mL against MCF-7 and ZR-75-1 (ER+) and 13.5 and 10.0 g/mL against MDA MB-231 andHS 587-1 (ER-), respectively. Furthermore, 15 also showed potent activity against SK-BR-3 (ER-, HER2+)with an ED50 value of 0.10 g/mL. Our preliminary SAR studies showed that a methylated furan ring D andthe C-4 substituent in ring A are critical for anti-breast cancer activity. Further development of 1 and 15 asanti-breast cancer drug candidates is warranted.
g/mL against MCF-7 and ZR-75-1 (ER+) and 13.5 and 10.0 g/mL against MDA MB-231 andHS 587-1 (ER-), respectively. Furthermore, 15 also showed potent activity against SK-BR-3 (ER-, HER2+)with an ED50 value of 0.10 g/mL. Our preliminary SAR studies showed that a methylated furan ring D andthe C-4 substituent in ring A are critical for anti-breast cancer activity. Further development of 1 and 15 asanti-breast cancer drug candidates is warranted.