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

  • VOJÁČKOVÁ, P.; MICHALSKA, L.; NEČAS, M.; SHCHERBAKOV, D.; BOTTGER, E. C.; ŠPONER, J.; ŠPONER, J.; ŠVENDA, J. A Stereocontrolled Synthesis of (−)-Bactobolin A. J. Am. Chem. Soc. 2020142, 7306.

  • BOUDNÝ, M.; ZEMANOVÁ, J.; KHIRSARIYA, P.; BORSKÝ, M.; VERNER, J.; ČERNÁ, J.; OLTOVÁ, A.; ŠEDA, V.; MRÁZ, M.; JAROŠ, J.; Kašparková, M.; Jašková, Z.; Spunarová, M.; Brychtová, Y.; Souček, K.; Drápela, S.; Mayer, J.; Paruch, K.; Trbušek, M. Novel Chk1 inhibitor MU380 exhibits significant single-agent activity in TP53-mutated chronic lymphocytic leukemia cells. Haematologica 2019104, 2443.

  • NĚMEC, V.; HYLSOVÁ, M.; MAIER, L.; FLEGEL, J.; SIEVERS, S.; ZIEGLER, S.; SCHRÖDER, M. BERGER, B.-T.; CHAIKUAD, A.; VALČIKOVÁ, B.; ULDRIJAN, S.; DRÁPELA, S.; SOUČEK, K.; WALDMANN, H.; KNAPP, S.; PARUCH, K. Furo[3,2-b]pyridine: A novel privileged scaffold for highly selective kinase inhibitors and effective modulators of the Hedgehog pathway. Angew. Chem. Int. Ed. 201958, 1062.

  • HAVEL, Š.; KHIRSARIYA, P.; AKAVARAM, N.; PARUCH, K.; CARBAIN, B. Preparation of 3,4-substituted-5-aminopyrazoles and 4-substituted-2-aminothiazoles. J. Org. Chem. 201883, 15380.

  • VOJÁČKOVÁ, P.; ChALUPA, D.; PRIEBOJ, J.; NEČAS, M.; ŠVENDA, J. Enantioselective Conjugate Additions of 2-Alkoxycarbonyl-3(2H)-furanones. Org. Lett. 2018, 20, 7085.

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.
  • Mgr. Štěpán Havel
  • Gorakhnath Rajaram Jachak
  • Bc. Klára Kejdová
  • Prashant Dineshbhai Khirsariya, Ph.D. MSc
  • Mgr. Lukáš Maier, Ph.D.
  • Ing. Monika Siekelová
  • Mgr. Jakub Švenda, Ph.D.
  • Pawel Szczepanik, MSc
  • Prabhakara Rao Tharra, Ph.D.

Principal Investigator

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

Assistant

Mgr. Gabriela Pavlíková
Mgr. Gabriela Pavlíková
Assistant