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

  • Bioorg Med Chem. 2014 Apr 1;22(7):2113-22. doi: 10.1016/j.bmc.2014.02.033.
Kartik W Temburnikar  1 ,  Sarah C Zimmermann  1 ,  Nathaniel T Kim  1 ,  Christina R Ross  2 ,  Christopher Gelbmann  3 ,  Christine E Salomon  3 ,  Gerald M Wilson  2 ,  Jan Balzarini  4 ,  Katherine L Seley-Radtke  5
Affiliations
  • 1. Department of Chemistry and Biochemistry, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
  • 2. Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 N. Greene Street, Baltimore, MD 21201, USA.
  • 3. Center for Drug Design, University of Minnesota, 516 Delaware St. SE, Minneapolis, MN 55455, USA.
  • 4. Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
  • 5. Department of Chemistry and Biochemistry, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA. Electronic address: [email protected].
PMID: 24631358 DOI: 10.1016/j.bmc.2014.02.033
Abstract

The in vitro evaluation of thieno[3,2-d]pyrimidines identified halogenated compounds 1 and 2 with antiproliferative activity against three different Cancer cell lines. A structure activity relationship study indicated the necessity of the chlorine at the C4-position for biological activity. The two most active compounds 1 and 2 were found to induce Apoptosis in the leukemia L1210 cell line. Additionally, the compounds were screened against a variety of Other microbial targets and as a result, selective activity against several fungi was also observed. The synthesis and preliminary biological results are reported herein.

Keywords
Antifungal; Apoptosis; Cytostatic; Heterocyclic chemistry; Thieno[3,2-d]pyrimidine.