PUBLICATION
Pyrimidine Derivative, (E)-N-[4-(4-Chlorophenyl)-6-(4-Methylphenyl)Pyrimidin-2-yl]-1-(Furan-2-yl)Methanimine, Named BN5 Ameliorates Cognitive Dysfunction and Regulates esr1 and esr2b Expression in Female In Vivo Zebrafish Alzheimer Model
- Authors
- Aswinanand, B., Palani, K.N., Santhanam, S.D., Ramamurthy, K., Palaniappan, S., Arasu, M.V., Guru, A., Muthuramamoorthy, M., Kumaradoss, K.M., Arockiaraj, J.
- ID
- ZDB-PUB-251022-11
- Date
- 2025
- Source
- Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 20: 9494 (Journal)
- Registered Authors
- Keywords
- Alzheimer’s disease, Antioxidant, Aβ-plaques, Estrogen receptor, Scopolamine
- MeSH Terms
-
- Alzheimer Disease*/drug therapy
- Alzheimer Disease*/genetics
- Alzheimer Disease*/metabolism
- Animals
- Cognitive Dysfunction*/drug therapy
- Cognitive Dysfunction*/metabolism
- Disease Models, Animal
- Estrogen Receptor alpha*/biosynthesis
- Estrogen Receptor alpha*/genetics
- Estrogen Receptor beta*/biosynthesis
- Estrogen Receptor beta*/genetics
- Female
- Furans*/pharmacology
- Furans*/therapeutic use
- Imines*/pharmacology
- Imines*/therapeutic use
- Pyrimidines*/pharmacology
- Pyrimidines*/therapeutic use
- Zebrafish
- PubMed
- 41118046 Full text @ J. Neuroimmune Pharmacol.
Citation
Aswinanand, B., Palani, K.N., Santhanam, S.D., Ramamurthy, K., Palaniappan, S., Arasu, M.V., Guru, A., Muthuramamoorthy, M., Kumaradoss, K.M., Arockiaraj, J. (2025) Pyrimidine Derivative, (E)-N-[4-(4-Chlorophenyl)-6-(4-Methylphenyl)Pyrimidin-2-yl]-1-(Furan-2-yl)Methanimine, Named BN5 Ameliorates Cognitive Dysfunction and Regulates esr1 and esr2b Expression in Female In Vivo Zebrafish Alzheimer Model. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology. 20:9494.
Abstract
Alzheimer's disease (AD) is the most common form of dementia, characterized by a progressive decline in cognitive functions. It is more prevalent in women, especially after menopause, likely due to factors like longer life expectancy and hormonal changes. Current therapies focus on cholinesterase inhibitors, but recent studies suggest that pyrimidine derivatives hold promise as multi-target agents targeting complex mechanisms of AD. This study evaluated the potential of a pyrimidine derivative, (E)-N-[4-(4-chlorophenyl)-6-(4-methylphenyl)pyrimidin-2-yl]-1-(furan-2-yl)methanimine (named BN5), in a scopolamine (SCO)-induced female zebrafish model. SCO induces cognitive dysfunction mimicking AD conditions. BN5, particularly at a 60 µM concentration, significantly improved AD-related parameters, including anxiety, memory, shoaling, and social behaviour in vivo. Biochemical analyses supported these findings, as BN5 reversed SCO-induced changes in acetylcholinesterase (AChE) activity and oxidative stress markers, such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA), and γ-Aminobutyric acid (GABA) levels. Additionally, BN5 demonstrated positive regulation of neurotransmitter-related genes such as appb, bdnf, mbpa, and il-1β, essential for neural function and cognitive processes. It also upregulated estrogen receptor genes esr1 and esr2b, which have neuroprotective roles but are often downregulated in postmenopausal women due to hormonal changes. These results highlight the therapeutic potential of BN5, as it alleviates cognitive impairments through Aβ aggregation inhibition and addresses the decline in estrogen receptor activity, providing a targeted treatment option particularly beneficial for females, who are at greater risk of developing AD.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping