Antitumor agents. 272. Structure-activity relationships and in vivo selective anti-breast cancer activity of novel neo-tanshinlactone analogues.
Antitumor agents. 272. Structure-activity relationships and in vivo selective anti-breast cancer activity of novel neo-tanshinlactone analogues.
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DOI：
10.1021/jm1000858
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发表时间：
2010-03-11
影响因子：
7.3
通讯作者：
Lee KH
中科院分区：
文献类型：
--
作者：
Dong Y;Shi Q;Pai HC;Peng CY;Pan SL;Teng CM;Nakagawa-Goto K;Yu D;Liu YN;Wu PC;Bastow KF;Morris-Natschke SL;Brossi A;Lang JY;Hsu JL;Hung MC;Lee EY;Lee KH
Neo-tanshinlactone (1) and its previously reported analogs, such as 2, are potent and selective in vitro anti-breast cancer agents. The synthetic pathway to 2 was optimized from seven to five steps, with a better overall yield. Structure–activity relationships studies on these compounds revealed some key molecular determinants for this family of anti-breast agents. Several derivatives (19-21 and 24) exerted potent and selective anti-breast cancer activity with IC50 values of 0.3, 0.2, 0.1 and 0.1 μg/mL, respectively, against the ZR-75-1 cell lines. Compound 24 was two- to three-fold more potent than 1 against SK-BR-3 and ZR-75-1. Importantly, 21 exhibited high selectivity; it was 23 times more active against ZR-75-1 than MCF-7. Compound 20 had an approximately 12-fold ratio of SK-BR-3/MCF-7 selectivity. In addition, analog 2 showed potent activity against a ZR-75-1 xenograft model, but not PC-3 and MDA-MB-231 xenografts, as well as high selectivity against breast cancer cell line compared with normal breast tissue-derived cell lines. Further development of lead compounds 19-21 and 24 as clinical trial candidates is warranted.
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通讯作者：
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