Projects

  • Chiroptical, optical and magnetic probes for protein sensing based on cage metal complexes
    Project No. 778245 (H2020-MSCA-RISE-2017)

The CLATHROPROBES project is devoted to the design and development of novel, highly efficient chiroptical, luminescent, IR, NMR and EPR probes for sensing and structural studies of biomolecules based on cage metal complexes (clathrochelates and lacunar complexes of spatial trisdiiminate ligands with encapsulated 3d-metal ion) as molecular reporters. For successful design and synthesis of cage metal complexes, their complete structural and spectroscopic characterization, studies of their interactions with biomolecules and reporting properties, andtheir cytotoxicity and bioactivity in model systems, the project brings together researchers from four academic institutions and two industrial companies, representing six countries (PL, DE, UA, RU, RO, AUT). The participants will contribute to the project with different, highly specific, yet complementary expertise, namely in chemical synthesis of clathrochelate complexes (PBMR, INEOS RAS, FAU), identification and structural studies of compounds and materials (PBMR, INEOS RAS, FAU, UWR, UNIVIE, SPS), characterization of interactions between ligands/clathrochelates/materials and biomolecules by CD, UV-vis, fluorescence ITC, (UWR, FAU, PBMR, UNIVIE, SPS), IR, NMR (INEOS RAS) methodology, and biological studies (FAU). Joint efforts of participants of this multidisciplinary project will provide - the transfer of knowledge between scientists of different research areas, sectors and countries that will enhance level of their professional scientific/technical expertise, - training of young researchers, very important for their further scientific success or industrial career, - enhancement of research activity and network of participating Institutions, - new long-term collaborations between the partners, - increase of academia-industry interactions, so valuable for innovative ideas and discoveries, and pair scientific excellence with social awareness and understanding of current tasks and problems of science.

  • Metal complexes of indolo-quinolines,-bezazepines, -benzazocines and benzazonines as potential anticancer drugs
    Project No. P31293-N37

The project is aimed at investigation of the effects of replacement of 7-membered azepine ring in paullones by a 8- and 9-membered benzazocine and benzazonine, respectively, the locus of lactam unit in them and position of the indole basic unit vs lactam group on antiproliferative activity both in vitro and in vivo, as well as affinity to particular enzymes as possible targets for these potential anticancer drugs. Another issue to be elucidated is whether attachment of cell-penetrating homing peptides to highly cytotoxic scaffolds or nanoparticle drug formulations elaborated over the lifetime of the project can lead to their selective delivery to cancer cells and, consequently, markedly reduce the side effects. To achieve these ambitious goals the proposal brings together organic, inorganic and analytical chemists, biochemists, electrochemists, experts in mass spectrometry, protein crystallography, molecular modeling and oncology.

  • Antiproliferative hybrids and their metal complexes as topoisomerase II and hR2 ribonucleotide reductase (RNR) inhibitors
    FWF Project No. P28223-N34

Description: Design and synthesis of new hybrid systems based on (iso)chalcogensemicarbazones/aminoguanisones with tunable pharmacokinetic and pharmacodynamic properties as well as their transition metal complexes as potential chemotherapeutic agents oriented a priori towards topoisomerase IIα⁄β (topo IIα⁄β) and/or hR2 RNR as a cancer specific target.

The following papers have already been published:
 
  1.  Milunović, M. N. M.; Dobrova, A.; Novitchi, G.; Gligorijević, N.; Radulović, S.; Kožišek, J.; Rapta, P.; Enyedy, A. E.; Arion, V. B. Effects of terminal substitution and iron coordination on antiproliferative activity of L-proline-salicylaldehyde Thiosemicarbazone Hybrids. Eur. J. Inorg. Chem. 2017, 4773‒4783.
  2. Sîrbu, A.; Palamarciuc, O.; Babak, M. V.; Lim, J. M.; Ohui, K.; Enyedy, E. A.; Shova, S.; Darvasiová, D.; Rapta, P.; Ang, W. H.; Arion, V. B. Copper(II) thiosemicarbazone complexes induce marked ROS accumulation and promote nrf2-mediated antioxidant response in highly resistant breast cancer cells. Dalton Trans. 2017, 46, 3833‒3847.  
  3. Zaltariov, M. F.; Hammerstad, M.; Arabshahi, H. J.; Jovanović K.; Richter, K. W.; Cazacu, M.; Shova, S.; Balan, M.; Andersen, N. H.; Radulović, S.; Reynisson, J.; Andersson, K. K.; Arion, V. B. New iminodiacetate-thiosemicarbazone hybrids and their copper(II) complexes are potential ribonucleotide reductase R2 inhibitors with high antiproliferative activity. Inorg. Chem. 2017, 56, 3532‒3549.
  4. Bacher, F.; Dömötör, O.; Enyedy, E.A.; Filipovic, L.; Radulovic, S.; Smith, G.S.; Arion, V.B. Complex formation reactions of gallium(III) and iron(III/II) with L-proline-thiosemicarbazone hybrids: A comparative study. Inorg. Chim. Acta 2017, 455, 505‒513.
  5. Dobrova, A.; Platzer, S.; Bacher, F.; Milunovic, M. N. M.; Dobrov, A.; Spengler, G.; Enyedy, E.A.; Novitchi, G.; Arion, V. B. Structure‒antiproliferative activity studies on L-proline- and homoproline-4-N-pyrrolidine-3-thiosemicarbazone hybrids and their nickel(II), palladium(II) and copper(II) complexes. Dalton Trans. 2016, 45, 13427‒13439.