Structural design, molecular modeling studies and synthesis of novel pyrrolidine derivatives as ligand candidates to target alpha-7-nicotinic acetylcholine receptors focusing on Alzheimer’s disease.

Alzheimer’s disease (AD) is one of the most common types of neurodegenerative disorders and the development of an effective treatment remains a challenge for researchers today. The nicotinic acetylcholine receptors (nAChRs) which are closely related with AD, especially the alpha-7-nAChR, are involved in neuroprotective effects (effects which may result in the salvage, recovery or regeneration of the nervous system), and play a key role in information processing and affecting the beta-amyloid protein-induced neurotoxicity. This research project proposes 88 novel pyrrolidine derivatives, structurally based on lobeline, varenicline, and nicotine drugs. Molecular docking studies involving the alpha-7-nAChR and the 88 novel compounds will be performed by a Master’s student in a structure-based virtual screening approach prior to my arrival, in order to select the best 8 compounds for synthesis. I will be performing the synthesis, isolation, purification, and characterization of the 8 optimal compounds in order to obtain enough quantity and acceptable purity for them to then be sent for pharmacological evaluation (at the Federal University of Rio de Janeiro) of the binding affinity and intrinsic activity against the alpha-7-nAChRs.

Faculty Supervisor:

Neil Burford

Student:

Partner:

Universidade Estadual Paulista "Julio de Mesquita Filho"

Discipline:

Life Sciences

Sector:

Pharmaceuticals; Health and Related Sciences & Technology

University:

University of Victoria

Program: