Abstract: Alzheimer's disease (AD) is the most common form of dementia, affecting nearly 10% of individuals over the age of 65 and nearly 50% of those over the age of 85. It is responsible for incapacitation of the individual by degrading cognitive functions, and its evolution leads the individual to death after a few years. It is characterized by brain degeneration triggered by several factors. One of the triggering factors is in the acetylcholine system. There is a decrease in the count of this neurotransmitter in individuals with this disease. The involvement of endogenous metal ions such as iron, copper, and zinc has also been involved in neurodegeneration mechanisms, in which there is the formation of radical species that cause oxidative stress, with important contribution of the neutrophil-derived enzyme myeloperoxidase, forming lesions in the neuronal cytoplasm and functional deficiency of neurons. In the present work, we report the evaluation of seventeen Camphor hydrazone derivatives 3a—3q, prepared in accordance with our previous work, as probable inhibitors of myeloperoxidase (MPO), acetylcholinesterase (AChE), and free radical-scavenging, to be used as potential agents against AD. Nine compounds showed significant activity against MPO. Among them, 3j and 3k had 78.4 and 53.9 μM (IC₅₀), respectively. Three compounds showed stronger activity, 3d, 3k, and 3l with EC₅₀ of 15.2, 21.3, and 14.4 µM, respectively, for free radical-scavenging activity, being similar to the standard quercetin (12.8 µM). All the final compounds were analyzed for drug-likeness. With exception for 3e and 3p, all were suitable on all filters evaluated. These results show that the compounds of hydrazone class are promising in the search for potential candidates for new agents against AD.

Key words: Camphor, hydrazones, acetylcholinesterase, myeloperoxidase, inhibitors