Antiproliferative activities of halogenated pyrrolo[3,2-d]pyrimidines

Kartik W. Temburnikar, Christina R. Ross, Gerald M. Wilson, Jan Balzarini, Brian M. Cawrse, Katherine L. Seley-Radtke

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


In vitro evaluation of the halogenated pyrrolo[3,2-d]pyrimidines identified antiproliferative activities in compounds 1 and 2 against four different cancer cell lines. Upon screening of a series of pyrrolo[3,2-d]pyrimidines, the 2,4-Cl compound 1 was found to exhibit antiproliferative activity at low micromolar concentrations. Introduction of iodine at C7 resulted in significant enhancement of potency by reducing the IC50 into sub-micromolar levels, thereby suggesting the importance of a halogen at C7. This finding was further supported by an increased antiproliferative effect for 4 as compared to 3. Cell-cycle and apoptosis studies conducted on the two potent compounds 1 and 2 showed differences in their cytotoxic mechanisms in triple negative breast cancer MDA-MB-231 cells, wherein compound 1 induced cells to accumulate at the G2/M stage with little evidence of apoptotic death. In contrast, compound 2 robustly induced apoptosis with concomitant G2/M cell cycle arrest in this cell model.

Original languageEnglish (US)
Pages (from-to)4354-4363
Number of pages10
JournalBioorganic and Medicinal Chemistry
Issue number15
StatePublished - Jul 23 2015
Externally publishedYes


  • Apoptosis
  • Cell cycle arrest
  • Cytostatic
  • Heterocyclic chemistry
  • Thieno[3,2-d]pyrimidine

ASJC Scopus subject areas

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


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