Professor Ingebrigt Sylte
Molecular Modeling Group of Medical Pharmacology and Toxicology, Department of Medical Biology, University of Tromsø (Norway)
The scientific cooperation with Molecular Modeling Group of Medical Pharmacology and Toxicology, Department of Medical Biology, University of Tromsø, headed by Professor Ingebrigt Sylte has began in 2008 with submission of a project entitled “Creating an academia-based platform to discover substances acting on serotonergic or glutamatergic systems as potential new antidepressant or anxiolytic drugs” to the Polish-Norwegian Research Fund. The project was finally granted and was launched at the end of 2009. Since then, a very close and intensive joint research on a number of topics already resulted with 5 publications (see 10, 16, 18–20), 26 conference communications, and more papers are in preparation and will be soon submitted. Very frequent personal contacts during PNRF project Steering Committee Meetings and scientific conferences along with intensive young researchers exchange (overall 16 short-term visits) tighten relationships and multiply experience and capacities of both groups. Our common interests are: exploration of ligand-receptor interactions by molecular docking and molecular dynamics, homology modeling of GPCRs, quantitative structure-activity relationships, similarity search, exploration of chemical
space by cheminformatics methods.
(1) Warszycki, D.; Mordalski, S.; Kristiansen, K.; Kafel, R.; Sylte, I.; Chilmonczyk, Z.; Bojarski, A. J. A Linear Combination of Pharmacophore Hypotheses as a New Tool in Search of New Active Compounds – An Application for 5-HT1A Receptor Ligands. PLoS. One. 2013, 8, e84510
(2) Gabrielsen, M.; Wolosewicz, K.; Zawadzka, A.; Kossakowski, J.; Nowak, G.; Wolak, M.; Stachowicz, K.; Siwek, A.; Ravna, A. W.; Kufareva, I.; Kozerski, L.; Bednarek, E.; Sitkowski, J.; Bocian, W.; Abagyan, R.; Bojarski, A. J.; Sylte, I.; Chilmonczyk, Z. Synthesis, Antidepressant Evaluation and Docking Studies of Long-Chain Alkylnitroquipazines as Serotonin Transporter Inhibitors. Chem. Biol. Drug Des 2013, 81, 695-706
(3) Jaronczyk, M.; Wolosewicz, K.; Gabrielsen, M.; Nowak, G.; Kufareva, I.; Mazurek, A. P.; Ravna, A. W.; Abagyan, R.; Bojarski, A. J.; Sylte, I.; Chilmonczyk, Z. Synthesis, in vitro binding studies and docking of long-chain arylpiperazine nitroquipazine analogues, as potential serotonin transporter inhibitors. Eur. J. Med. Chem. 2012, 49C, 200-210.
(4) Witowska-Jarosz, J.; Jaronczyk, M.; Mazurek, A. P.; Sylte, I.; Bojarski, A. J.; Chilmonczyk, Z.; Jarosz, M. Mass-spectrometric studies of new 6-nitroquipazines-serotonin transporter inhibitors. Anal. Bioanal. Chem. 2012, 402, 537-541.
(5) Gabrielsen, M.; Kurczab, R.; Ravna, A. W.; Kufareva, I.; Abagyan, R.; Chilmonczyk, Z.; Bojarski, A. J.; Sylte, I. Molecular mechanism of serotonin transporter inhibition elucidated by a new flexible docking protocol. Eur. J. Med. Chem. 2012, 47, 24-37.
(6) Mordalski, S.; Kosciolek, T.; Kristiansen, K.; Sylte, I.; Bojarski, A. J. Protein binding site analysis by means of structural interaction fingerprint patterns. Bioorg. Med. Chem. Lett. 2011, 21, 6816-6819
(7) Kurczab, R.; Nowak, M.; Chilmonczyk, Z.; Sylte, I.; Bojarski, A. J. The development and validation of a novel virtual screening cascade protocol to identify potential serotonin 5-HT(7)R antagonists. Bioorg. Med. Chem. Lett. 2010, 20, 2465-2468
Professor Marcello Leopoldo
Medicinal Chemistry Department Faculty of Pharmacy University of Bari (Italy)
The main research interests of Professor Marcello Leopoldo are: the synthesis, preliminary pharmacological evaluation, and structure-activity relationship studies of ligands for neurotransmitter receptors. In particular, His studies have been focused on the identification of selective ligands for serotonin 5-HT1A, dopamine D4 and dopamine D3 receptors.
Recently, the major field of interest was the identification of selective agents for serotonin 5-HT7 receptor. The studies have led to the identification of a class of potent 5-HT7 agonists that have been patented. Two of the agonists are currently included into the “Tocris
Bioscience” catalogue (LP-44: Cat. No. 2534; LP-12: Cat. No. 2925).
Since Professor Leopoldo’s research fields are complementary with studies carried out in our Department, he was invited by the Director, Prof. Krzysztof Wędzony, to visit the Institute of Pharmacology. The visit finally took place in May 2010 and resulted, among others, in signing a formal cooperation between both Institutions in Dec 2011. Joint research so far concerns design and synthesis of fluorescent probes for the study of G-protein coupled receptors and design and synthesis of new ligands for serotonin receptors.
(1) Lacivita, E.; De Giorgio, P.; Patarnello, D.; Niso, M.; Colabufo, N. A.; Berardi, F.; Perrone, R.; Satala, G.; Duszynska, B.; Bojarski, A. J.; Leopoldo, M. Towards metabolically stable 5-HT receptor ligands: a study on 1-arylpiperazine derivatives and related isosters. Exp. Brain Res. 2013, 230, 569-582
Professor Franck Suzenet
Institut de Chimie Organique et Analytique, University of Orléans (France)
The cooperation with Professor Franck Suzenet originated from the thesis of Eduard Badarau, who synthezied a number of potential ligands of 5-HT7 receptors. There are already 3 papers published from this subject (see 5, 9, 11) and further collaboration is continued under Polish Academy of Sciences and French National Center for Scientific Research (CNRS) research agreement, which however covers only visits costs. One joint manuscript is in preparation and more new sub-projects are under development.
(1) Badarau, E.; Putey, A.; Suzenet, F.; Joseph, B.; Bojarski, A.; Finaru, A.; Guillaumet, G. New insights into homopiperazine-based 5-HT1A/5-HT7R ligands: synthesis and biological evaluation. J. Enzyme Inhib. Med. Chem. 2010, 25, 301-305
(2) Badarau, E.; Bugno, R.; Suzenet, F.; Bojarski, A. J.; Finaru, A. L.; Guillaumet, G. SAR studies on new bis-aryls 5-HT7 ligands: Synthesis and molecular modeling. Bioorg. Med. Chem. 2010, 18, 1958-1967.
(3) Badarau, E.; Suzenet, F.; Bojarski, A. J.; Finaru, A. L.; Guillaumet, G. Benzimidazolone-based serotonin 5-HT(1A) or 5-HT(7)R ligands: Synthesis and biological evaluation. Bioorg. Med. Chem. Lett. 2009, 19, 1600-1603
Professor Maria Angela Siracusa
Dipartimento di Scienze del Farmaco Università degli Studi di Catania (Italy)
Scope of research:
- Development of new arylpiperazine derivatives as 5-HT7 ligands
Professor Bernard Testa
Pharmacy Department, University Hospital Centre, Lausanne (Switzerland)
Scope of research:
- Study of the phenomena of dissolvance and emergence of properties of molecular structures considered as complex systems at different stages of the organization
- Changes in the content of information of complex systems in the simplified evolutionary models
(1) Testa, B.; Bojarski, A. J. Molecules as complex adaptative systems: constrained molecular properties and their biochemical significance. Eur. J. Pharm. Sci. 2000, 11 Suppl 2, S3-S14
(2) Testa, B.; Kier, L. B. ; Bojarski, A. J. Molecules and Meaning: How Do Molecules Become Biochemical Signals? SEED 2002, 2, 84-101.
(3) Bojarski, A. J.; Nowak, M.; Testa, B. Conformational constraints on side chains in protein residues increase their information content. Cell. Mol. Life Sci. 2003, 60, 2526-2531.
(4) Testa, B.; Vistoli, G. ; Pedretti, A.; Bojarski, A. J.; Nowak, M. Computational explorations of the property space of biomolecules. Proceedings of the COMPLEXITY IN THE LIVING 2004 A Problem-Oriented
Approach 2005, 193-207.
(5) Bojarski, A. J.; Nowak, M.; Testa, B. Conformational Fluctuations versus Constraints in Amino Acid Side Chains: The Evolution of Information Content from Free Amino Acids to Proteins. Chem. Biodivers. 2006,
(6) Testa, B.; Bojarski, A. J. Variation, natural selection, and information content–a simulation. Chem. Biodivers. 2007, 4, 2458-2472.
(7) Testa, B.; Bojarski, A. J. Simulations in evolution. II. Relative fitness and the propagation of mutants. Chem. Biodivers. 2009, 6, 356-368.
(8) Testa, B.; Vistoli, G. ; Pedretti, A.; Bojarski, A. J. Atomic diversity, molecular diversity, and chemical diversity: the concept of chemodiversity. Chem. Biodivers. 2009, 6, 1145-1151.
Professor Lucjan Strekowski
Department of Chemistry, Georgia State University, Atlanta (USA)
Scope of research:
- Synthesis of new derivatives of 4-mono-and / or 4,6-disubstituted derivatives of 2 – (N-metylopiperazino) pyrimidin as new 5-HT7 ligands
- Quantitative structure-activity relationships in the group of 4-aminoquinoline derivatives antagonizing the immunostimulatory effect of the CpG oligodeoxynucleotides
(1) Strekowski, L.; Say, M.; Henary, M.; Ruiz, P.; Manzel, L.; Macfarlane, D. E.; Bojarski, A. J. Synthesis and activity of substituted 2-phenylquinolin-4-amines, antagonists of immunostimulatory pG-oligodeoxynucleotides. J. Med. Chem. 2003, 46, 1242-1249.
(2) Paliakov, E.; Henary, M.; Say, M.; Patterson, S. E.; Parker, A.; Manzel, L.; Macfarlane, D. E.; Bojarski, A. J.; Strekowski, L. Fujita-Ban QSAR analysis and CoMFA study of quinoline antagonists of immunostimulatory CpG-oligodeoxynucleotides. Bioorg. Med. Chem. 2007, 15, 324-332.
(3) Saczewski, J.; Paluchowska, A.; Klenc, J.; Raux, E.; Barnes, S.; Sullivan, S.; Duszyńska, B.; Bojarski, A. J.; Strekowski, L. Synthesis of 4-substituted 2-(4-methylpiperazino)pyrimidines and quinazoline analogs as serotonin 5-HT2A receptor ligands. J. Heterocyclic Chem. 2009, 46, 1259-1265.