Synthesis of Novel Thymine-β-lactam Hybrids and Evaluation of Their Antitumor Activity

Nicola Piens; Rob De Vreese; Nympha De Neve; Kristof Van Hecke; Jan Balzarini; Norbert De Kimpe; Matthias D’hooghe

doi:10.1055/s-0033-1338647

Synthesis, Table of Contents

Synthesis 2014; 46(18): 2436-2444
DOI: 10.1055/s-0033-1338647

paper

Synthesis of Novel Thymine-β-lactam Hybrids and Evaluation of Their Antitumor Activity

Nicola Piens

^aSynBioC Research Group, Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium Fax: +32(9)2646221 Email: matthias.dhooghe@UGent.be

,

Rob De Vreese

^aSynBioC Research Group, Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium Fax: +32(9)2646221 Email: matthias.dhooghe@UGent.be

,

Nympha De Neve

^aSynBioC Research Group, Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium Fax: +32(9)2646221 Email: matthias.dhooghe@UGent.be

,

Kristof Van Hecke

^bDepartment of Inorganic and Physical Chemistry, Faculty of Sciences, Ghent University, Krijgslaan 281-S3, 9000 Ghent, Belgium

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Jan Balzarini

^cRega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium

,

Norbert De Kimpe

^aSynBioC Research Group, Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium Fax: +32(9)2646221 Email: matthias.dhooghe@UGent.be

,

Matthias D’hooghe*

^aSynBioC Research Group, Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium Fax: +32(9)2646221 Email: matthias.dhooghe@UGent.be

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Abstract

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Abstract

Trimethylene-tethered thymine-β-lactam and thymine-bis-β-lactam chimeras were prepared as novel classes of hybrid systems through selective mono- or bis-N-alkylation of thymine with cis-1-(3-bromopropyl)-β-lactams. In addition, acidic methanolysis of the β-lactam nucleus in these systems provided an entry into the class of thymine-β-amino ester hybrids. A selection of the newly synthesized hybrid compounds was assessed for their antiviral activity, cytotoxicity, and cytostatic activity, revealing a significant cytostatic effect of one of the derivatives against murine leukemia and human T-lymphocyte tumor cells.

Key words

molecular hybridization - β-lactams - thymine - acidic methanolysis - antitumor agents

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References

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