Synthesis and evaluation of novel monocyclic beta-lactams as neuroprotectors

In the nervous system, glutamate acts as the principal excitatory neurotransmitter. However, high doses of glutamate in the synapse can result in nervous cell damage and even cell death, which is associated with diseases such as Parkinson's and Alzheimer's. Traditionally, beta-lactam compounds were used strictly as antimicrobial agents. Recent studies, however, have demonstrated their utility in another area---protection against excitotoxicity. Thus far, the mechanism responsible for their neuroprotective effects is still not understood. This project focuses on the development and testing of a library of beta-lactams designed to act as possible neuroprotective agents. Unlike penicillin and cephalosporin, these are monocyclic and have a conformationally flexible group at the C4 position of the lactam ring. They also contain various lipophilic substituents at the C3 position. The neuroprotective ability of the newly synthesized beta-lactams will be tested with the possibility of both expanding the class of compounds used as neuroprotective agents, as well as potentially aiding in the understanding of the mechanism responsible for their neuroprotective effects.