New multifunctional AChE inhibitor drug prototypes protect against Aβ-induced memory deficit

• Published in: Neurological sciences 2020-02, Vol.41 (2), p.451-455
• Main Authors: Bellozi, Paula M. Q., Campos, Alline C., Viegas, Flávia P. D., Silva, Matheus de F., Machado, Rafael P., Vaz, Sarah M., Riquiel, Mariana M., Carneiro-Junior, Wellerson de O., Lima, Isabel V. de A., Saliba, Soraya W., Vaz, Gabriela Neves, Viegas, Claudio, de Oliveira, Antônio C. P.
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase; Alzheimer Disease - drug therapy; Alzheimer's disease; Amyloid; Amyloid beta-Peptides - metabolism; Animals; Brief Communication; Cholinesterase Inhibitors - pharmacology; Cognition Disorders - drug therapy; Cognitive ability; Disease Models, Animal; Drug development; Hippocampus; Medicine; Medicine & Public Health; Memory; Memory - drug effects; Memory Disorders - chemically induced; Memory Disorders - drug therapy; Mice, Inbred C57BL; Neurodegenerative diseases; Neurofibrillary tangles; Neurology; Neuroprotection; Neuroprotective Agents - therapeutic use; Neuroradiology; Neurosciences; Neurosurgery; Pattern recognition; Peptide Fragments - pharmacology; Psychiatry
• ISSN: 1590-1874; 1590-3478
• DOI: 10.1007/s10072-019-04036-6

Alzheimer’s disease (AD) is the most incident neurodegenerative disorder, characterized by accumulation of extracellular amyloid-β (Aβ), intracellular neurofibrillary tangles, and cognitive impairment. The current available treatments are mainly based on the use of reversible acetylcholinesterase (AChE) inhibitors, which only ameliorate the cognitive deficits. However, it is important to develop disease-modifying drugs with neuroprotective effects in order to hamper the progression of the disease. Here, we describe the effect of four promising new drugs with additional protective characteristics on AD-associated memory changes. C57Bl/6 mice treated with the compounds received an intra-hippocampal injection of Aβ1-40 and were submitted to the novel object recognition test, to evaluate memory recovery. All the compounds prevented memory loss. Compounds PQM-56 (4c) and PQM-67 (4g) showed the best profile of memory recovery, representing potential drug candidates for AD treatment.