Research focus

The research in our laboratory focuses on development of synthetic methods and strategies for preparation of structurally non-trivial small molecules for applications in biomedical research. Specifically, our project includes:

  • Development of potent inhibitors of certain „non-routine“ kinases (CLK, HIPK).
  • Synthesis of new forskolin-based modulators of adenylyl cyclases
  • Identification inhibitors of selected DNA repair pathways (nucleases Mre11 and Mus81).
  • Preparation of new small-molecules probes of cell differentiation, and fluorescent probes for biological systems.

Research objectives

  • Total synthesis of new analogs of forskolin and testing their activity against human adenylyl cyclases.
  • SAR development around the existing proprietary inhibitors of nucleases MRE11 and Mus81; identification of sub-micromolar inhibitors.
  • Synthesis and biological profiling of new carbocyclic C-nucleosides.

Main partners

  • Max Planck Institute for Molecular Physiology, Dortmund, Germany
  • University of Oxford, Oxford, United Kingdom
  • University of Oslo, Oslo, Norway

Technological equipment

Infrastructure for modern organic synthesis:

  • HPLC with UV
  • MS and CAD detection
  • Microwave Reactor
  • High Pressure Reactor

Offered services and expertise

  • Organic synthesisof small-molecule organic compounds of medium complexity.
  • Medicinal chemistry - optimization of early leads.
  • Separation of racemic mixtures by HPLC on chiral stationary phase on semipreparative scale.

Top publications

  • JORDA, J., PARUCH, K., KRYŠTOF, V. Cyclin-dependent kinase Inhibitors Inspired by Roscovitine: Purine Bioisosteres. Current Pharmaceutical Design 2012, 18(20), 2974-2980.
  • AMARO, M., BREZOVSKY, J., KOVÁČOVÁ, S., MAIER, L., CHAOUPKOVA, R., SYKORA, J., PARUCH, K., DAMBORSKÝ, J., HOF, M. Are Time-Dependent Fluorescence Shifts at the Tunnel Mouth of Haloalkane Dehalogenase Enzymes Dependent on the Choice of the Chromophore?Journal of Physical Chemistry B 2013, 117(26), 7898-7906.
  • BRAHMKSHATRIYA, P., DOBES, P., FANFRLIK, J., REZAC, J., PARUCH, K., BRONOWSKA, A., LEPSIK, M., HOBZA, P. Quantum Mechanical Scoring: Structural and Energetic Insights into Cyclin-Dependent Kinase 2 Inhibition by Pyrazolo[1,5-a]pyrimidines. Current Computer - Aided Drug Design 2013, 9(1), 118-129.
  • AMARO, M., BREZOVSKÝ, J., KOVÁČOVÁ, S., SÝKORA, J., BEDNÁŘ, D., NĚMEC, V., LIŠKOVÁ, V., KURUMBANG, N., BEERENS, K., CHALOUPKOVÁ, R., PARUCH, K., HOF, M., DAMBORSKÝ, J. Site-specific analysis of protein hydration based on unnatural amino Acid fluorescence. Journal of the American Chemical Society 2015, 137(15), 4988-4992.
  • HILL, N., PARUCH, K., ŠVENDA, J. Late-stage annulativeconvergency in natural product synthesis. Tetrahedron 2016, 72, 3345-3368.

Other selected results

Substituted furo [3,2-b]pyridines - new compounds with targeted biological activity which effectively inhibit the activity of PIM kinases. PIM kinases are proteins whose overproduction is characteristic for prostate cancer cells, and some forms of leukemia and lymphomas. Compounds can be used for prostate cancer treatment. The compounds are covered by Czech patentCZ 305472.

Team members

  • doc. Mgr. Kamil Paruch, Ph.D.
  • Mgr. Gabriela Pavlíková
  • Benoit Jean-Pierre Carbain, Ph.D.
  • RNDr. David Chalupa
  • Mgr. Štěpán Havel
  • Gorakhnath Rajaram Jachak
  • Prashant Dineshbhai Khirsariya, Ph.D. MSc
  • Mgr. Lucyna Michalska
  • Mgr. Václav Němec
  • Mgr. Lucie Ovčáčková
  • Mgr. Jakub Švenda, Ph.D.
  • Pawel Szczepanik, MSc

Principal Investigator

doc. Mgr. Kamil Paruch, Ph.D.
doc. Mgr. Kamil Paruch, Ph.D.
Principal Investigator

Assistant

Mgr. Gabriela Pavlíková
Mgr. Gabriela Pavlíková
Assistant