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

Kartik W Temburnikar; Sarah C Zimmermann; Nathaniel T Kim; Christina R Ross; Christopher Gelbmann; Christine E Salomon; Gerald M Wilson; Jan Balzarini; Katherine L Seley-Radtke

doi:10.1016/j.bmc.2014.02.033

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. Epub 2014 Mar 3.

Authors

Kartik W Temburnikar¹, Sarah C Zimmermann¹, Nathaniel T Kim¹, Christina R Ross², Christopher Gelbmann³, Christine E Salomon³, Gerald M Wilson², Jan Balzarini⁴, Katherine L Seley-Radtke⁵

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].

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Antifungal Agents / chemical synthesis
Antifungal Agents / chemistry
Antifungal Agents / pharmacology*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Bacillus subtilis / drug effects*
Cell Cycle / drug effects
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Fungi / drug effects*
Humans
Microbial Sensitivity Tests
Molecular Structure
Pyrimidines / chemical synthesis
Pyrimidines / chemistry
Pyrimidines / pharmacology*
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Anti-Bacterial Agents
Antifungal Agents
Antineoplastic Agents
Pyrimidines

Abstract

Publication types

MeSH terms

Substances

Grants and funding