Medicinal Chemistry - Natural products’ inspired molecules. Coordinator: Bisi

Design and synthesis of bioactive small molecules, as potential drug candidates, based on oxa- and azaheterocyclic scaffolds, related to different classes of natural compounds (such as flavonoids and coumarins)

Research themes

Research involves the design and synthesis of bioactive small molecules as potential drug candidates. Scaffolds are mainly oxa- and azaheterocycles, related to different classes of natural products. These molecules can be considered as privileged structures and carriers that, when differently functionalized with appropriate pharmacophore moieties, can tailor the activity towards one or more targets involved in complex pathologies.

Main research themes are related to the development of molecules able to modulate the activities of:

  • enzymes such as cholinesterases, BACE-1, GSK-3beta, FAAH and cannabinoids receptors for the treatment of neurodegenerative disorders (Alzheimer’s disease)
  • cytochromes P450 involved in the biosynthesis of estrogens and of estrogen receptors as antitumor agents
  • cytochromes P450 involved in the biosynthesis of corticosteroids for the treatment of related pathologies
  • enzymes involved in tumor progression (Hsp90, carbonic anhydrase) and multiple drug resistance (MDR)
  • key enzymes for the development of tropical parasitic diseases such as malaria, leishmanial infections and trypanosomiasis (Fab I, GAPDH, TR).

Internship projects

Internship for the preparation of a degree thesis has a duration of more or less 8 months and involves the synthesis, purification and structural characterization of bioactive small molecules. The student takes part in one of the ongoing projects of the research group, in particular neurodegeneration, tumor or parasitic neglected diseases. 4/6 positions are available per year.

 

Main publications

Bisi, A.; Cappadone, C.; Rampa, A.; Farruggia, G.; Sargenti, A.; Belluti, F.; Di Martino, R. M. C.; Malucelli, E.; Meluzzi, A.; Iotti, S.; Gobbi, S. Coumarin derivatives as potential antitumor agents: Growth inhibition, apoptosis induction and multidrug resistance reverting activity. Eur. J. Med. Chem. (2017), 127, 577-585. Doi: 10.1016/j.ejmech.2017.01.020

Montanari, S.; Scalvini, R.; Bartolini, M.; Belluti, F.; Gobbi, S.; Andrisano, V.; Ligresti, A., Di Marzo V. Rivara, S.; Mor, M.; Bisi, A.; Rampa, A. Fatty Acid Amide Hydrolase (FAAH), Acetylcholinesterase (AChE), and Butyrylcholinesterase (BuChE): Networked Targets for the Development of Carbamates as Potential Anti-Alzheimer's Disease Agents. J. Med. Chem. (2016), 59, 6387-6406. doi: 10.1021/acs.jmedchem.6b00609

Ortalli, M.; Ilari, A.; Colotti, G.; De Ionna, I.; Battista, T.; Bisi, A.; Gobbi, S.; Rampa, A.; Di Martino, R. M. C.; Gentilomi, G.A.; Varani, S.; Belluti, F. Identification of chalcone-based antileishmanial agents targeting trypanothione reductase. Eur. J. Med. Chem. (2018), 152, 527-541. doi: 10.1016/j.ejmech.2018.04.057

Gobbi, S.; Hu, Q.; Zimmer, C.; Belluti, F.; Rampa, A.; Hartmann, R. W.; Bisi, A. Drifting of heme-coordinating group in imidazolylmethylxanthones leading to improved selective inhibition of CYP11B1. Eur. J. Med. Chem. (2017), 139, 60-67. doi: 10.1016/j.ejmech.2017.07.078

Bisi, A.; Arribas, R. L.; Micucci, M.; Budriesi, R.; Feoli, A.; Castellano, S.; Belluti, F.; Gobbi, S.; de Los Rios, C.; Rampa, A. Polycyclic maleimide-based derivatives as first dual modulators of neuronal calcium channels and GSK-3β for Alzheimer's disease treatment. Eur. J. Med. Chem. (2019), 163, 394-402. Doi: 10.1016/j.ejmech.2018.12.003

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