(+)-Dehydroabietylamine derivatives target triple-negative breast cancer

Taotao Ling, My Tran, Miguel A. González, Lekh Nath Gautam, Michele Connelly, Rachael K. Wood, Iram Fatima, Gustavo Miranda-Carboni, Fatima Rivas

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Breast cancer remains the leading cause of cancer-related death among women. The invasive triple-negative subtype is unresponsive to estrogen therapy, and few effective treatments are available. In search of new chemical scaffolds to target this disease, we conducted a phenotypic screen against the human breast carcinoma cell lines MDA-MB-231, MA11, and MCF-7 using terrestrial natural products. Natural products that preferentially inhibited proliferation of triple-negative MDA-MB-231 cells over estrogen receptor-positive cells were further studied; herein we focused on the abietanes. The activity of the abietane carnosol prompted us to generate a focus library from the readily available (+)-dehydroabietylamine. The lead compound 61 displayed a promising EC50 of 9.0 μM against MDA-MB-231 and our mechanistic studies indicate it induced apoptosis, which was associated with activation of caspase-9 and -3 and the cleavage of PARP. Here we describe our current progress towards this promising therapeutic candidate.

Original languageEnglish (US)
Pages (from-to)9-13
Number of pages5
JournalEuropean Journal of Medicinal Chemistry
Volume102
DOIs
StatePublished - Aug 3 2015

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Abietane Diterpenes
Triple Negative Breast Neoplasms
Biological Products
Cells
Lead compounds
Derivatives
Caspase 9
Scaffolds
Estrogen Receptors
Breast Neoplasms
Estrogens
Chemical activation
Apoptosis
Caspase 3
Libraries
Therapeutics
Cell Line
dehydroabietylamine
Neoplasms

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Ling, T., Tran, M., González, M. A., Gautam, L. N., Connelly, M., Wood, R. K., ... Rivas, F. (2015). (+)-Dehydroabietylamine derivatives target triple-negative breast cancer. European Journal of Medicinal Chemistry, 102, 9-13. https://doi.org/10.1016/j.ejmech.2015.07.034

(+)-Dehydroabietylamine derivatives target triple-negative breast cancer. / Ling, Taotao; Tran, My; González, Miguel A.; Gautam, Lekh Nath; Connelly, Michele; Wood, Rachael K.; Fatima, Iram; Miranda-Carboni, Gustavo; Rivas, Fatima.

In: European Journal of Medicinal Chemistry, Vol. 102, 03.08.2015, p. 9-13.

Research output: Contribution to journalArticle

Ling, Taotao ; Tran, My ; González, Miguel A. ; Gautam, Lekh Nath ; Connelly, Michele ; Wood, Rachael K. ; Fatima, Iram ; Miranda-Carboni, Gustavo ; Rivas, Fatima. / (+)-Dehydroabietylamine derivatives target triple-negative breast cancer. In: European Journal of Medicinal Chemistry. 2015 ; Vol. 102. pp. 9-13.
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