Nucleoside and nucleotide analogues for biomedical applications

The group established in spring 2010 partly continues traditions and scientific program of the parent team of Prof. Antonín Holý - Antimetabolites of Nucleic Acid Components.

The present research in the Group is targeted to design and synthesis of novel biologically active compounds focused to nucleoside and nucleotide analogs, especially acyclic nucleoside phosphonates (ANPs) as potential antiviral, cytostatics, antiparasitic (antimalarial) and immunomodulatory agents.

A special attention is paid to improvement of biological activity and pharmacokinetic profile of acyclic nucleoside phosphonates for antiviral and cancer chemotherapy by increasing their delivery into cells in target tissue. This aim is achieved by transformation of ANPs to appropriate prodrugs. At present, design and synthesis of new types of prodrugs of our biologically active compounds represent one of the main activities of the Group.

Besides acyclic nucleoside phosphonate chemistry, we deal also with syntheses of modified nucleobases and analogs of nucleosides. All new compounds are tested for cytostatic effects on cell cultures and submitted to general antiviral screening against DNA viruses, RNA viruses and retroviruses. A particular attention is paid also to study of antitumor activity of compounds bound to their inhibitory activity towards thymidine phosphorylase, an enzyme playing a key role in angiogenesis in tumors.

A special part of our research is chemistry of triazine compounds, particularly 5-azacytosine and its nucleoside and nucleotide analogs. This chemistry, originally developed at IOCB by Dr. Alois Pískala and resulting later in U.S.A. in clinical application of our compounds as entirely unique antileukemic therapeutics (Vidaza, Dacogen) still provides many possibilities for new discoveries.