Date of Award

8-1-2013

Document Type

Campus Access Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

Béla Török

Second Advisor

Marianna Török

Third Advisor

Jonathan Rochford

Abstract

Several diverse group of molecules were designed and synthesized to test their biological potential as Phospholipase D (PLD) inhibitors and anti-Alzheimer’s disease agents. Phosphatidic acid (PA), known as an important precursor for many essential cellular molecules, is a product of cleavage of glycerophospholipids substrates by PLD enzymes. Overexpression of PLD has been found in several human cancers. PLD inhibitors based on 1,3-disubstituted-4-amino-pyrazolopyrimidine core structure were synthesized and exhibited strong inhibition of the purified PLD enzyme with IC50 values in the nanomolar range. The other target, Alzheimer’s disease is the most prevalent neurodegenerative disorder associated with the loss of cholinergic neurotransmission and the presence of amyloid deposits and neurofibrillary tangles in the brain. Several designed sulfonamide, chalcone and coumarin derivatives showed excellent inhibition of cholinesterases (AChE, BuChE), amyloid beta (Aβ) self-assembly and the disassembled preformed Aβ oligomers and fibrils.

Comments

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