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Research group coordinated by prof. Marco De Amici  

Permanent staff: Prof. Marco De Amici, Prof. Clelia Dallanoce

Research Associates: Dr. Marco Maspero

The research group has complementary skills in the field of medicinal chemistry, synthetic organic chemistry and molecular modeling. The main research lines at present under investigation are the following.

1) Design, synthesis and structure/activity relationships of small molecules and peptides selectively acting at specific neuronal nicotinic acetylcholine receptor (nAChR) subtypes
The derivatives under study are novel heterocyclic compounds (mainly obtained through pericyclic and/or cross-coupling reactions as key steps) or modified peptides structurally related to natural toxins. This research aims at finding out new molecular entities able to selectively interact with specific nAChR populations, thus being potentially useful derivatives for the therapeutic intervention in CNS pathologies, nicotine addiction, pain and inflammation.

2) Design, synthesis and structure/activity relationships of allosteric modulators of muscarinic acetylcholine receptors (mAChRs)
The main achievements of this research are related to the discovery of quaternary bisammonioalkane salts able to simultaneously interact with the orthosteric and the allosteric binding site of the M2 mAChR subtype. The detailed study of the pharmacological profile evidenced for some of these new bitopic muscarinic ligands the modulation of receptor efficacy together with the activation of pathway-specific intracellular signaling.

3) Design, synthesis and biological evaluation of bifunctional compounds
We designed, prepared and tested various sets of putative bifunctional ligands, i.e. compounds whose molecular skeleton is characterized by pharmacophoric elements able to promote the interaction with both nicotinic receptor subtypes and dopaminergic receptor subtypes. This research project aims at disclosing novel ligands endowed with neuroprotective and neurotrophic properties as well as pharmacological tools for the treatment of nicotine addiction or Parkinson’s disease.

Scientific partners
In the framework of the above summarized scientific activities, the research group cooperates with researchers belonging to the following international and national institutions: Pharmacology and Toxicology Section, Institute of Pharmacy and Molecular, Cellular and Pharmacobiology Section, Institute of Pharmaceutical Biology (University of Bonn);  Department of Pharmaceutical Chemistry, Institute of Pharmacy and Department of Pharmacology and Toxicology (University of Wűrzburg); School of Chemistry (University of Bristol); Istituto Mario Negri (Milan); the National Research Council (CNR) of Milan, the Universities of Milan, Modena and Reggio Emilia, Parma, Brescia, Florence, Bologna, Genua and Rome.

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