Student Presenter(s): Annette Pietraru
Faculty Mentor: Jole Fiorito
School/College: Arts and Sciences, Old Westbury

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is characterized by initial memory impairment resulting in cognitive decline. AD affects speech, behavior, visuospatial orientation, and the motor system. The main hallmarks of AD include amyloid plaques and neurofibrillary tangles. Due to the complexity of disease, efficient therapies may require pharmacologic agents that are capable of targeting several targets simultaneously. The multi-target directed ligand (MTDL) approach uses a single drug molecule that is able to interact with multiple targets. Through our research, we aimed to synthesize new MTDLs that can be used to target phosphodiesterase type 5 (PDE5) and histone acetyltransferase (HAT), two enzymes found to play a significant role in AD. Previous studies (2018-ISRC project) showed that a combination treatment (PDE5 inhibitor and HAT modulator) in mice improved synaptic communication between neurons in the hippocampus. We designed and synthesized new molecules by combining structural moieties of PDE5 inhibitors and HAT modulators through chemical reactions using commercially available starting materials. Intermediates of the synthesis of the final products were obtained and assessed for purity and composition using NMR, IR, and LC/MS. Future steps will include purifying the final products and testing them for PDE5 and HAT enzymatic activity.