UO DRUG DISCOVERY

L’UO si occupa di Progettazione, ottimizzazione della struttura, sintesi e dosamento di composti di interesse terapeutico.

Responsable (RUO)
Prof. Marco Mor
Dipartimento di Farmacia
Viale delle Scienze 27/a – 43124 Parma
e-mail: marco.mor@unipr.it
CV

Competences
The OU provides technical and scientific expertise in medicinal chemistry, in its computational aspects (research and design of new bioactive molecules, in silico evaluation of toxicological risks), synthetic (development of the synthesis of new compounds, producing lots of compounds for studies in animal models) and bioanalytical (dosamento in biological fluids, evaluation of pharmacokinetic parameters and degradation metabolic drugs).
Questa UO offre competenze di chimica farmaceutica, nei suoi aspetti computazionali (ricerca e progettazione di nuove molecole bioattive, valutazione in silico dei rischi tossicologici), sintetici (messa a punto della sintesi di nuovi composti, produzione di lotti di composti per studi in modelli animali) e bioanalitici (dosamento in fluidi biologici, valutazione di parametri farmacocinetici e degradazioni metaboliche di farmaci).

(Prof. Marco Mor) In particular, it has specific expertise in the following areas:
EGFR inhibitors with cytotoxic activity;
modulators of lipid metabolism of endocannabinoids and related compounds;
compounds acting on the system melatoninerigico.

(Prof. Gabriele Costantino) In particular, it has specific expertise in the following areas:
compounds with antibacterial effect;
compounds active on the central nervous system.
Brevetti

  1. D. PIOMELLI, A. DURANTI, A. TONTINI, M. MOR, G. TARZIA.; “Modulation of anxiety through blockade of anandamide hydrolysis”; WO/2004/033422
    Domanda di deposito internazionale: 7 ottobre 2003 (PCT/US2003/031844).
    Concessione in USA: 13 Febbraio 2007, N. 7176201
  2. G. GOBBI, M. MOR, S. RIVARA, F. FRASCHINI, G. TARZIA, A. BEDINI, G. SPADONI.; “Novel melatonin ligands having antidepressant activity as well as sleep inducing properties”; WO/2007/079593
    Domanda di deposito internazionale: 12 gennaio 2007 (PCT/CA2007/000055).
  3. D. PIOMELLI, G. TARZIA, M. MOR, A. DURANTI, A. TONTINI.; "Compositions and methods of inhibiting N-acylethanolamine-hydrolyzing acid amidase"; WO/2009/049238
    Domanda di deposito internazionale: 10 ottobre 2008 (PCT/US2008/079621).
  4. R. ALFIERI, F. BORDI, C. CARMI, A. CAVAZZONI, A. LODOLA, M. MOR, P. G. PETRONINI, S. VEZZOSI; "Composti inibitori irreversibili di egfr con attivita' antiproliferativa"; PCT/IB2009/055980.
    Domanda di deposito Nazionale: 29 dicembre 2008 (MI2008A002336).
    Domanda di deposito internazionale: 29 dicembre 2009 (PCT/IB2009/055980).
  5. G.COSTANTINO, L.AMORI- R. SCHWARCZ Derivatives of nicotinic acid N-oxie, their preparation and thier use as inhibitors of 3HAO . PCREP2011050670

Research collaboration:

  • Les Laboratoires Servier
  • The Royal Institution for the Advancement of Learning/McGill University
  • Istituto Europeo di Oncologia
  • Maryland Psichiatric Research Center, University of Maryland
  • Institute of Organic Synthesis, Riga, Lettonia

  • Subunit:
    Synthesis of Biologically Active compounds and experimental characterization of their interaction with biomolecules
    Questa subunità si occupa di realizzare progetti di ricerca precompetitiva e industriale nell’ambito della progettazione e sintesi di molecole organiche ad attività biologica.

    Competences:
    This OU provides the expertise to carry out precompetitive and industrial projects aimed at designing and synthesizing organic molecules endowed of biological activity as new drugs and carriers for advanced therapies (antitumoral, genetic and epigenetic therapies) and at optimizing new synthetic pathways also environmentally-friendly.


    Expertise
    The subunit specially has expertise in the following fields: i) organic synthesis; ii) chemical modification of carbohydrates and small peptides comprising conjugation to multivalent scaffolds; iii) design and synthesis of small ligands for proteins and nucleic acids; iv) development of gene-delivery and drug-delivery systems also endowed of site-specificity (targeted delivery); v) setting of diagnostic systems for the detection of specific proteic or DNA markers; vi) use of advanced physical-chemistry techniques (NMR, AFM, CD, DLS, Fluorescence) for the characterization of molecules and their interaction with bio-macromolecules.

    (Prof. Alessandro Casnati:)
    • Carbohydrate synthesis and modification
    • Glycosylated multivalent ligands for the interaction with proteins (lectins) also for tumor-targeting
    • New surfactants as gene-delivery systems and gene-therapy
    • Inhibitors of adhesion of pathogenic agents (toxins bacteria, viruses etc..)
    • Targeted drug-delivery systems.

    (Prof. Roberto Corradini)
    • Design and synthesis of bioactive molecules for modulation of gene expression
    • Synthesis of bioactive peptides and peptidic carriers
    • Study of the interactions between synthetic molecules and biopolymers;
    • Diagnostic and theranostic methods based on nucleic acid recognition.
    • Anti-miR and Anti-gene agents
    • Chirality and Chiroptical methods

    Recent References

    Prof. Alessandro Casnati

  • Arosio, D.; Fontanella, M.; Baldini, L.; Mauri, L.; Bernardi, A.; Casnati, A.; Sansone, F.; Ungaro, R. A Synthetic Divalent Cholera Toxin Glycocalix[4]arene Ligand Having Higher Affinity than Natural GM1 Oligosaccharide J. Am. Chem. Soc., 2005, 127, 3660 – 3661. DOI: 10.1021/ja0444029
  • Cacciapaglia, R.; Casnati, A.; Mandolini, L.; Peracchi, A.; Reinhoudt, D. N.; Salvio, R.; Sartori, A.; Ungaro, R. Efficient and Selective Cleavage of RNA Oligonucleotides by Calix[4]arene-Based Synthetic Metallonucleases J. Am. Chem. Soc., 2007, 129, 12512-12520. DOI: 10.1021/ja0737366
  • André, S.; Sansone, F.; Kaltner, H.; Casnati, A.; Kopitz, J.; Gabius, H.-J.; Ungaro, R. Calix[n]arene-based Glycoclusters: Bioactivity of Thiourea-linked Galactose/Lactose Moieties as Inhibitors of Binding of Medically Relevant Lectins to a Glycoprotein and Cell Surface Glycoconjugates and Selectivity among Human Adhesion/Growth Regulatory Galectins ChemBioChem, 2008, 9, 1649-1661. DOI: 10.1002/cbic.200800035
  • Sansone, F.; Casnati A. Multivalent Glycocalixarenes for Recognition of Biological Macromolecules: Glycocalyx Mimics Capable of Multitasking, Chem. Soc. Rev., 2013, 42, 4623-4639. DOI: 10.1039/c2cs35437c
  • Bagnacani, V.; Franceschi, V.; Bassi, M.; Lomazzi, M.; Donofrio, G.; Sansone, F.; Casnati, A. Ungaro, R. Arginine clustering on calix[4]arene macrocycles as novel strategy for improving cell penetration and DNA delivery Nature Commun. 2013, 4, 1721. DOI:10.1038/ncomms2721.
  • Ungaro R.; Casnati A.; Donofrio G.; Sansone F.; Bagnacani V., Derivati calixarenici funzionalizzati per la Transfezione cellulare, Brevetto italiano MI2011A001532, Depositato il 11/08/2011, IT 2011-MI1532A, Aug 11, 2011; Ungaro R.; Casnati A.; Donofrio G.; Sansone F.; Bagnacani V., Preparation of functionalized calixarene derivatives for cell transfection, WO 2013021355A1, Feb 14, 2013 WO 2012-IB54041, Aug 8, 2012

  • Prof. Roberto Corradini

  • Aiba,Y.; Hamano, Y.; Kameshima, W.; Araki, Y.; Wada, T.; Accetta, A.; Sforza, S.; Corradini, R.; Marchelli, R.; Komiyama M. PNA–NLS conjugates as single-molecular activators of target sites in double-stranded DNA for site-selective scission Org. Biomol. Chem., 2013, 11, 5233-5238.
  • Brognara, E.; Fabbri, E.; Aimi, F.; Manicardi, A.; Bianchi, N.; Finotti, A.; Breveglieri, G.; Borgatti, M.; Corradini, R. Marchelli, R. Gambari R. Peptide nucleic acids targeting miR-221 modulate p27Kip1 expression in breast cancer MDA-MB-231 cells. Int. J. Oncol. 2012, 41(6), 2119-2127.
  • Manicardi, A.; Fabbri, E.; Tedeschi, T.; Sforza, S.; Bianchi, N.; Brognara, E.; Gambari, R.; Marchelli, R.; Corradini R. Cellular uptake, biostability and anti-miR-210 activity of chiral arginine-PNA in leukemic K562 cells. ChemBiochem 2012, 13, 1327 – 1337.
  • Tonelli, R.; Mcintyre, A.; Camerin, C.; Walters, Z. S.; Di Leo, K.; Selfe, J.; Purgato, S.; Missiaglia, E.; Tortori, A.; Astolfi, A.; Renshaw, J.; Taylor, K.R.; Serravalle, S.; Bishop, R.; Nanni, C.; Valentijn, L.J ; Faccini, A.; Leuschner, I.; Formica, S.; Reis-Filho, J.S.; Ambrosini, V.; Thway, K.; Franzoni, M.; Summersgill, B.; Marchelli, R.; Hrelia, P.; Cantelli-Forti, G.; Fanti, S.; Corradini, R.; Pession, A.; Shipley J. Antitumor Activity of Sustained N-Myc Reduction in Rhabdomyosarcomas and Transcriptional Block by Antigene Therapy. Clinical Cancer Res 2012, 18,796-807.
  • Corradini, R.; Tedeschi, T.; Sforza, S.; Marchelli R. 2012. Electronic Circular Dichroism of Peptide Nucleic acids and their analogues in “Advances in Chiroptical Methods” (Editors: Nina Berova, Prasad Polavarapu, Koji Nakanishi, and Robert W. Woody) Volume 2. Chapter 2.IV.5, John Wiley and Sons Inc, (United States). Pages 587-614.
  • Corradini, R.; Sforza, S.; Tedeschi, T.; Totsingan, F.; Manicardi, A.; Marchelli R. Peptide nucleic acids with a structurally biased backbone. Updated review and emerging challenges Curr Top Med Chem 2011 , 11, 1535-1554.