Antitumor Agents. 272. Structure-Activity Relationships and In Vivo Selective Anti-Breast Cancer Activity of Novel Neo-tanshinlactone Analogues

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Title:	Antitumor Agents. 272. Structure-Activity Relationships and In Vivo Selective Anti-Breast Cancer Activity of Novel Neo-tanshinlactone Analogues
Authors:	(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);洪明奇(Mien-Chie Hung);(Lee EY);(Lee KH)*
Contributors:	醫學院癌症生物學研究所;中國附醫院長室
Date:	2010-02
Issue Date:	2010-09-27 15:48:08 (UTC+8)
Abstract:	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.
Relation:	JOURNAL OF MEDICINAL CHEMISTRY 53():2299-2308
Appears in Collections:	[Graduate Institute of Cancer Biology] Journal articles

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