- The ultimate aim of the research project is to search for novel biologically active compounds as potential drug candidates, analogues active against neoplasia or diseases of viral origin. To focus predominantly on drug candidates applicable to virus-resistant (clinical) mutants in AIDS or hepatitis B, and to poxviruses.
- To design and synthesize novel analogues of acyclic nucleoside phosphonates (ANP) with potential biological activity, specifically those derived from open-ring series, isosteric compounds of the same structural group, benzo analogues, symmetrical disubstituted open-ring phosphonates and multifunctional phosphonates, 5-alkyl analogues of HPMPT and fluorine-bearing ANP’s.
- To elucidate mode of action, selectivity and kinetics of biologically active analogues (antimetabolites) of nucleosides and nucleotides - their interaction with specific targets on the molecular level.
- To search for immunomodulatory activity of nucleotide phosphonate analogues (ANP) and its contribution to the antiviral and/or anticancer activity of bioactive molecules.
- To search for new potential antineoplastic agents designed on the basis of analogues of nucleic acid constituents, with special attention to multiple drug resistance (MDR).
- To develop novel synthetic methodologies for modified purine and pyrimidine nucleobases, their simplified aromatic analogues, as well as the corresponding base-modified nucleosides and nucleotides and C-nucleosides and screening of their cytostatic and antiviral activity.
- To develop a new synthetic methodology for preparation of di- and triterpene analogs. In further stages of the project the essential part will be also a rational design of the target compounds based on activity-structure relationship studies data.
- To analyze molecular mechanisms of the development of viral resistance to protease inhibitors and design, synthesize and test novel compounds active against resistant virus species.
- To decipher molecular mechanism of retroviral capsid assembly with the aim to develop novel approaches to the design of virostatics.
- To develop diagnostics and therapy for prostatic cancer and other tumors (astrocytomas) based on the enzyme glutamate carboxypeptidase II which is expressed in above mentioned tumors.
- To investigate compounds active against opportunistic infections occurring in AIDS or immunosuppressed patients (e.g. analogues of naturally occurring lactones active against fungal pathogens).
- To develop specific drug transport to the cell nucleus making use of artificial viral capsides.
- To develop drug (and prodrug) formulations for specific (transdermal, oral) applications of polar compounds.
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