On December 15, 2021, Ip, Fanny C. F.; Fu, Guangmiao; Yang, Fengzhi; Kang, Fangyuan; Sun, Peiran; Ling, Choi Ying; Cheung, Kit; Xie, Fangzhou; Hu, Yueqing; Fu, Lei; Ip, Nancy Y. published an article.Category: chlorides-buliding-blocks The title of the article was A tacrine-tetrahydroquinoline heterodimer potently inhibits acetylcholinesterase activity and enhances neurotransmission in mice. And the article contained the following:
Cholinergic neurons are ubiquitous and involved in various higher brain functions including learning and memory. Patients with Alzheimer′s disease exhibit significant dysfunction and loss of cholinergic neurons. Meanwhile, such cholinergic deficits can be potentially relieved pharmacol. by increasing acetylcholine. Acetylcholinesterase (AChE) inhibitors have been used to improve cholinergic transmission in the brain for two decades and have proven effective for alleviating symptoms in the early stages of Alzheimer′s disease. Therefore, the search for AChE inhibitors for drug development is ongoing. The enzymic pocket of AChE has long been the target of several drug designs over the last two decades. The peripheral and catalytic sites of AChE are simultaneously bound by several dimeric mols., enabling more-efficient inhibition. Here, we used 6-chlorotacrine and the tetrahydroquinolone moiety of huperzine A to design and synthesize a series of heterodimers that inhibit AChE at nanomolar potency. Specifically, 6-[3-(6-chloro-1,2,3,4-tetrahydro-acridin-9-ylamino)propylamino]-5,6,7,8-tetrahydro-1H-quinolin-2-one inhibits AChE with an IC50 < 1 nM and spares butyrylcholinesterase. Administration of 6-[3-(6-chloro-1,2,3,4-tetrahydro-acridin-9-ylamino)propylamino]-5,6,7,8-tetrahydro-1H-quinolin-2-one to mouse brain slices restores synaptic activity impaired by pirenzepine, a muscarinic M1-selective antagonist. Moreover, oral administration of 6-[3-(6-chloro-1,2,3,4-tetrahydro-acridin-9-ylamino)propylamino]-5,6,7,8-tetrahydro-1H-quinolin-2-one to C57BL/6 mice enhances hippocampal long-term potentiation in a dose-dependent manner and is detectable in the brain tissue. All these data supported that 6-[3-(6-chloro-1,2,3,4-tetrahydro-acridin-9-ylamino)propylamino]-5,6,7,8-tetrahydro-1H-quinolin-2-one is a potential cognitive enhancer and is worth for further exploration. The experimental process involved the reaction of 2-Amino-4-chlorobenzoic acid(cas: 89-77-0).Category: chlorides-buliding-blocks
The Article related to tacrine tetrahydroquinoline heterodimer acetylcholinesterase inhibitor, cognitive function, dementia, electrophysiological recordings, hybrid, synaptic plasticity, Placeholder for records without volume info and other aspects.Category: chlorides-buliding-blocks
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics