61982-89-6Relevant articles and documents
Antitumor agents. 272. Structure-activity relationships and in vivo selective anti-breast cancer activity of novel neo-tanshinlactone analogues
Dong, Yizhou,Shi, Qian,Pai, Huei-Chen,Peng, Chieh-Yu,Pan, Shiow-Lin,Teng, Che-Ming,Nakagawa-Goto, Kyoko,Yu, Donglei,Liu, Yi-Nan,Wu, Pei-Chi,Bastow, Kenneth F.,Morris-Natschke, Susan L.,Brossi, Arnold,Lang, Jing-Yu,Hsu, Jennifer L.,Hung, Mien-Chie,Lee, Eva Y.-H. P.,Lee, Kuo-Hsiung
experimental part, p. 2299 - 2308 (2010/08/07)
Neo-tanshinlactone (1) and its previously reported analogues, such as 2, are potent and selective in vitro antibreast 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 antibreast agents. Several derivatives (19-21 and 24) exerted potent and selective antibreast 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 2- to 3-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, analogue 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.
