Synthesis of Novel Acyclic Nucleoside Analogues with Anti-Retroviral Activity

Abstract

A series of novel acyclic thymine nucleoside analogues were prepared by the Mitsunobu reaction from appropriately protected chiral triols. The enantiomeric triols were obtained from substituted γ-lactone acids, prepared by asymmetric oxidation of 3-substituted-1,2-cyclopentanediones. The cytotoxic activity of new analogues was evaluated on MCF-7 human breast cancer and HeLa cells, and antiviral activities on human immunodeficiency virus type 1 and hepatitis C virus models. The synthesized compounds revealed specific anti-retroviral activity and no cytotoxic side effects.

Keywords:

• Acyclic nucleosides
• anti-retroviral activity
• human immunodeficiency virus type 1
• hepatitis C virus

Acknowledgments

The authors are grateful to the Estonian Ministry of Education and Research (Grant No: 0142725s06), the Centre of Excellence in Chemical Biology, the EU European Regional Development Fund 3.2.0101.08-0017, and the AS Competence Centre for Cancer Research for their support.

Notes

*The number of viable cells in negative control samples (treated with DMSO alone) was taken as 100%. Cell viability is presented as a ratio (in percentage) of number of viable cells in experimental (treated with tested compound) to that in DMSO treated control cells.

**The OD_{540 nm} of DMSO-treated control cells was taken as 100%. Cell viability is presented as a ratio (in percentage) of the OD_{540 nm} of cells treated with the tested compounds to the OD_{540 nm} of DMSO-treated cells.