Mitotic arrest of breast cancer MDA-MB-231 cells by a halogenated thieno[3,2-d]pyrimidine

Christina R. Ross, Kartik Temburnikar, Gerald M. Wilson, Katherine L. Seley-Radtke

Research output: Contribution to journalArticle

Abstract

Halogenated thieno[3,2-d]pyrimidines exhibit antiproliferative activity against a variety of cancer cell models, such as the mouse lymphocytic leukemia cell line L1210 in which they induce apoptosis independent of cell cycle arrest. Here we assessed these activities on MDA-MB-231 cells, a well-established model of aggressive, metastatic breast cancer. While 2,4-dichloro[3,2-d]pyrimidine was less toxic to MDA-MB-231 cells than previously observed in the L1210 model, flow cytometry analysis showed that MDA-MB-231 cell death involved arrest at the G2/M stage of the cell cycle. Conversely, the introduction of bromine at C7 of the 2,4-dichloro[3,2-d]pyrimidine eliminated cell type-dependent differences in cytotoxicity or cell cycle status. Together, these data indicate that a substituent at C7 can profoundly modify the cytotoxic mechanism of halogenated thieno[3,2-d]pyrimidines in a cell type-specific manner.

Original languageEnglish (US)
Pages (from-to)1715-1717
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume25
Issue number8
DOIs
StatePublished - Apr 15 2015
Externally publishedYes

Fingerprint

Cells
Breast Neoplasms
Pyrimidines
Cell Cycle
Lymphoid Leukemia
Bromine
Flow cytometry
Poisons
Cell death
Cytotoxicity
Cell Cycle Checkpoints
Flow Cytometry
Cell Death
pyrimidine
Apoptosis
Cell Line
Neoplasms

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Mitotic arrest of breast cancer MDA-MB-231 cells by a halogenated thieno[3,2-d]pyrimidine. / Ross, Christina R.; Temburnikar, Kartik; Wilson, Gerald M.; Seley-Radtke, Katherine L.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 25, No. 8, 15.04.2015, p. 1715-1717.

Research output: Contribution to journalArticle

Ross, Christina R. ; Temburnikar, Kartik ; Wilson, Gerald M. ; Seley-Radtke, Katherine L. / Mitotic arrest of breast cancer MDA-MB-231 cells by a halogenated thieno[3,2-d]pyrimidine. In: Bioorganic and Medicinal Chemistry Letters. 2015 ; Vol. 25, No. 8. pp. 1715-1717.
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