Antitumor agents. 272. Structure-activity relationships and in vivo selective anti-breast cancer activity of novel neo-tanshinlactone analogues

Yizhou Dong, Qian Shi, Huei Chen Pai, Chieh Yu Peng, Shiow Lin Pan, Che Ming Teng, Kyoko Nakagawa-Goto, Donglei Yu, Yi Nan Liu, Pei Chi Wu, Kenneth F. Bastow, Susan L. Morris-Natschke, Arnold Brossi, Jing Yu Lang, Jennifer L. Hsu, Mien Chie Hung, Eva Y H P Lee, Kuo Hsiung Lee

Research output: Contribution to journalArticle

53 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2299-2308
Number of pages10
JournalJournal of Medicinal Chemistry
Volume53
Issue number5
DOIs
Publication statusPublished - Mar 11 2010
Externally publishedYes

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Structure-Activity Relationship
Antineoplastic Agents
Breast Neoplasms
Heterografts
Cell Line
Inhibitory Concentration 50
Neoplasms
Breast
Clinical Trials
neotanshinlactone

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

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.

In: Journal of Medicinal Chemistry, Vol. 53, No. 5, 11.03.2010, p. 2299-2308.

Research output: Contribution to journalArticle

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, EYHP & Lee, KH 2010, 'Antitumor agents. 272. Structure-activity relationships and in vivo selective anti-breast cancer activity of novel neo-tanshinlactone analogues', Journal of Medicinal Chemistry, vol. 53, no. 5, pp. 2299-2308. https://doi.org/10.1021/jm1000858
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. / Antitumor agents. 272. Structure-activity relationships and in vivo selective anti-breast cancer activity of novel neo-tanshinlactone analogues. In: Journal of Medicinal Chemistry. 2010 ; Vol. 53, No. 5. pp. 2299-2308.
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AU - Teng, Che Ming

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