Antitumor agents. 254. Synthesis and biological evaluation of novel neo-tanshinlactone analogues as potent anti-breast cancer agents

Xihong Wang, Kyoko Nakagawa-Goto, Kenneth F. Bastow, Ming Jaw Don, Yun Lian Lin, Tian Shung Wu, Kuo Hsiung Lee

研究成果: Article同行評審

79 引文 斯高帕斯(Scopus)

摘要

In our previous study, neo-tanshinlactone (1) showed potent and selective anti-breast cancer activity. To explore the SAR of 1, nine analogues (15-18, 24-28) were designed and synthesized. Together with 1 and tamoxifen (TAM), all newly synthesized compounds and some intermediates were evaluated for in vitro anticancer activity against several human tumor cell lines. Compounds without a ring D did not show promising activity, while compounds with a methylated furan ring D showed better activity than those with unsubstituted furan or hydroxy-dihydrofuran rings. Among all newly synthesized compounds, compound 15 with an ethyl group at the 4-position showed the best activity and selectivity with ED50 values of 0.45 and 0.18 μg/mL against MCF-7 and ZR-75-1 (ER+) and 13.5 and 10.0 μg/mL against MDA MB-231 and HS 587-1 (ER-), respectively. Furthermore, 15 also showed potent activity against SK-BR-3 (ER-, HER2+) with an ED50 value of 0.10 μg/mL. Our preliminary SAR studies showed that a methylated furan ring D and the C-4 substituent in ring A are critical for anti-breast cancer activity. Further development of 1 and 15 as anti-breast cancer drug candidates is warranted.

原文English
頁(從 - 到)5631-5634
頁數4
期刊Journal of Medicinal Chemistry
49
發行號18
DOIs
出版狀態Published - 2006 九月 7

All Science Journal Classification (ASJC) codes

  • 分子醫學
  • 藥物發現

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