Research group: Cristina Lanni, Marco Racchi, Michele Catanzaro, Martina Pansini, Alessandra Roggeri

Oxidative stress and inflammation are common features of different disorders and the identification of new drugs acting on these pathways is an open field of research because of their potential application in different pathologies.
The project is based on an innovative strategy: nature may represent a structural “muse”. Natural products offer great chemical diversity and may be a rich source of therapeutics being of inspiration to create new bioactive compounds. The idea to synthesize new nature-inspired hybrids raised by the knowledge that hydroxycinnamoyl recurring motif, present in many natural polyphenols, has been shown to modulate several pathways related to aging and dementia. In addition, diallyl sulfides, garlic-derived organosulfur compounds carrying allyl mercaptan moieties, are able to counteract oxidative stress through antioxidant enzyme expression. A set of molecules has been characterized as versatile tools for investigating the molecular mechanisms potentially involved in aging and dementia, coming to identify a catechol derivative, with remarkable antiaggregating ability and antioxidant properties. In the pursuit of more effective molecules, systematic modifications of this compound have been performed, and new natural compounds as Nrf2 inducers have been preliminarily identified, showing a better antioxidant activity than molecules already known in literature, such as curcumin or a known Nrf2 activator, such as dimethyl fumarate.
The project is aimed to investigate the contribution of some of these nature-inspired molecules in preventing and/or rescuing the inflammaging and redoxaging by deepening their specific mechanism of action. In particular we will investigate their potential activity in RAGE, NFkB and Nrf2 signalling pathways.

Recent Publications:

• Simoni E, Serafini MM, Bartolini M, Caporaso R, Pinto A, Necchi D, Fiori J, Andrisano V, Minarini A, Lanni C*, Rosini M*. Nature-Inspired Multifunctional Ligands: Focusing on Amyloid-Based Molecular Mechanisms of Alzheimer’s Disease. ChemMedChem. 11(12):1309-17; 2016. *co-authorship
• Simoni E, Serafini MM, Caporaso R, Marchetti C, Racchi M, Minarini A, Bartolini M, Lanni C, Rosini M. Targeting the Nrf2/Amyloid-Beta Liaison in Alzheimer’s Disease: A Rational Approach. ACS Chem Neurosci. 8(7):1618-1627; 2017.
• Serafini MM, Catanzaro M, Rosini M, Racchi M, Lanni C. Curcumin in Alzheimer’s disease: Can we think to new strategies and perspectives for this molecule? Pharmacol Res.124:146-155; 2017.

Links:
http://dipsf.unipv.eu/site/home/research.html
https://www.researchgate.net/profile/Cristina_Lanni